Scholars@Duke
Michael S. Krangel

Michael S. Krangel

George Barth Geller Distinguished Professor of Immunology
Integrative Immunobiology
krang001@mc.duke.edu
Duke Box 3010, Durham, NC 27710
318 Jones Bldg, Durham, NC 27710

Selected Publications

RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire.

Journal Article Sci Immunol · March 15, 2024 Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4-CD8- double-negative (DN) to the CD4+CD8+ double-positive (DP) stage, but the physiological importance and mechanism of transcriptional up-regulation are unknown ... Full text Link to item Cite

Methods for Study of Mouse T Cell Receptor α and β Gene Rearrangements.

Journal Article Methods Mol Biol · 2023 Quantitative real-time PCR and next-generation sequencing (NGS) are invaluable techniques to analyze T cell receptor (Tcr) gene rearrangements in mouse lymphocyte populations. Although these approaches are powerful, they also have limitations that must be ... Full text Link to item Cite

E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.

Journal Article Front Immunol · 2023 V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins a ... Full text Link to item Cite

Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.

Journal Article J Exp Med · February 7, 2022 The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary ... Full text Link to item Cite

The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.

Journal Article Nat Commun · January 4, 2021 CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising ... Full text Link to item Cite

A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus.

Journal Article Nucleic Acids Res · September 25, 2020 The regulation of T cell receptor Tcra gene rearrangement has been extensively studied. The enhancer Eα plays an essential role in Tcra rearrangement by establishing a recombination centre in the Jα array and a chromatin hub for interactions between Vα and ... Full text Open Access Link to item Cite

RSSs set the odds for exclusion.

Journal Article J Exp Med · September 7, 2020 In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20200412) provide new insights into allelic exclusion. They demonstrate that Vβ-to-DβJβ rearrangement occurs stochastically on two competing Tcrb alleles, with suboptimal Vβ recombination signal ... Full text Link to item Cite

Hierarchical assembly and disassembly of a transcriptionally active RAG locus in CD4+CD8+ thymocytes.

Journal Article J Exp Med · January 7, 2019 Featured Publication Expression of Rag1 and Rag2 is tightly regulated in developing T cells to mediate TCR gene assembly. Here we have investigated the molecular mechanisms governing the assembly and disassembly of a transcriptionally active RAG locus chromatin hub in CD4+CD8+ ... Full text Link to item Cite

Diversification of the TCR β Locus Vβ Repertoire by CTCF.

Journal Article Immunohorizons · December 2018 Featured Publication The architectural protein CTCF regulates the conformation and recombination of antigen receptor loci. To study the importance of CTCF in Tcrb locus repertoire formation, we created a conditional knockout mouse line that deletes Ctcf early during thymocyte ... Full text Link to item Cite

A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus.

Journal Article Cell Rep · November 13, 2018 Featured Publication Tcrb locus V(D)J recombination is regulated by positioning at the nuclear periphery. Here, we used DamID to profile Tcrb locus interactions with the nuclear lamina at high resolution. We identified a lamina-associated domain (LAD) border composed of severa ... Full text Link to item Cite

On the Horizon.

Journal Article Immunohorizons · January 17, 2018 Full text Link to item Cite

Variable Extent of Lineage-Specificity and Developmental Stage-Specificity of Cohesin and CCCTC-Binding Factor Binding Within the Immunoglobulin and T Cell Receptor Loci.

Journal Article Front Immunol · 2018 Featured Publication CCCTC-binding factor (CTCF) is largely responsible for the 3D architecture of the genome, in concert with the action of cohesin, through the creation of long-range chromatin loops. Cohesin is hypothesized to be the main driver of these long-range chromatin ... Full text Link to item Cite

Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.

Journal Article Cell Rep · June 6, 2017 Featured Publication Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd ... Full text Link to item Cite

ImmunoHorizons, a New Home for Immunology Research

Journal Article ImmunoHorizons · January 1, 2017 Full text Cite

An Ectopic CTCF Binding Element Inhibits Tcrd Rearrangement by Limiting Contact between Vδ and Dδ Gene Segments.

Journal Article J Immunol · October 15, 2016 Featured Publication Chromatin looping mediated by the CCCTC binding factor (CTCF) regulates V(D)J recombination at Ag receptor loci. CTCF-mediated looping can influence recombination signal sequence (RSS) accessibility by regulating enhancer activation of germline promoters. ... Full text Link to item Cite

Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development.

Journal Article J Exp Med · August 22, 2016 Featured Publication T cell antigen receptor δ (Tcrd) variable region exons are assembled by RAG-initiated V(D)J recombination events in developing γδ thymocytes. Here, we use linear amplification-mediated high-throughput genome-wide translocation sequencing (LAM-HTGTS) to map ... Full text Link to item Cite

The Ties that Bind (the Igh Locus).

Journal Article Trends Genet · May 2016 Immunoglobulin heavy-chain locus V(D)J recombination requires a 3D chromatin organization which permits widely distributed variable (V) gene segments to contact distant diversity (D) and joining (J) gene segments. A recent study has identified key nodes in ... Full text Link to item Cite

Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53.

Journal Article J Immunol · March 15, 2016 Featured Publication Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used m ... Full text Link to item Cite

Inactivation of nuclear GSK3β by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response.

Journal Article Nat Commun · January 29, 2016 Featured Publication Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclea ... Full text Link to item Cite

A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRδ and TCRα repertoires.

Journal Article Nat Immunol · October 2015 Featured Publication The locus encoding the T cell antigen receptor (TCR) α-chain and δ-chain (Tcra-Tcrd) undergoes recombination of its variable-diversity-joining (V(D)J) segments in CD4(-)CD8(-) double-negative thymocytes and CD4(+)CD8(+) double-positive thymocytes to genera ... Full text Open Access Link to item Cite

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.

Journal Article J Exp Med · May 4, 2015 Featured Publication Rag1 and Rag2 gene expression in CD4(+)CD8(+) double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unkno ... Full text Link to item Cite

T-cell receptor α enhancer is inactivated in αβ T lymphocytes.

Journal Article Proc Natl Acad Sci U S A · April 7, 2015 Featured Publication The Tcra enhancer (Eα) is essential for Tcra locus germ-line transcription and primary Vα-to-Jα recombination during thymocyte development. We found that Eα is inhibited late during thymocyte differentiation and in αβ T lymphocytes, indicating that it is n ... Full text Link to item Cite

IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection

Journal Article Nature Immunology · March 19, 2015 Featured Publication Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (β-selection) of TCRβ+ CD4-CD8- double-negative stage 3 (DN3) and DN4 progenitor cells that differentiate into CD4+CD8+ double-positive (DP) thym ... Full text Cite

Specification of Vδ and Vα usage by Tcra/Tcrd locus V gene segment promoters.

Journal Article J Immunol · January 15, 2015 Featured Publication The Tcra/Tcrd locus undergoes V-Dδ-Jδ rearrangement in CD4(-)CD8(-) thymocytes to form the TCRδ chain of the γδ TCR and V-Jα rearrangement in CD4(+)CD8(+) thymocytes to form the TCRα-chain of the αβ TCR. Most V segments in the locus participate in V-Jα rea ... Full text Link to item Cite

Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.

Journal Article J Exp Med · January 12, 2015 Featured Publication Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unkno ... Full text Link to item Cite

Chromatin Dynamics and the Development of the TCRα and TCRδ Repertoires.

Journal Article Adv Immunol · 2015 Featured Publication The adaptive immune system allows vertebrates to orchestrate highly specific responses to a virtually unlimited milieu of antigens. Effective adaptive immune responses depend on the capacity of T and B lymphocytes to generate diverse repertoires of antigen ... Full text Link to item Cite

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G₁-phase lymphocytes.

Journal Article Mol Cell Biol · August 2014 Featured Publication The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G1-phase cells. Antigen receptor gene a ... Full text Link to item Cite

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

Journal Article Proc Natl Acad Sci U S A · November 26, 2013 Featured Publication Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that ... Full text Link to item Cite

Chromatin architecture, CCCTC-binding factor, and V(D)J recombination: managing long-distance relationships at antigen receptor loci.

Journal Article J Immunol · May 15, 2013 Featured Publication The rearrangement of T and B lymphocyte Ag receptor loci occurs within a highly complex chromosomal environment and is orchestrated through complex mechanisms. During the past decade, a large body of literature has highlighted the significance of chromatin ... Full text Link to item Cite

The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration.

Journal Article Immunity · December 14, 2012 Featured Publication Histone 3 lysine 4 trimethylation (H3K4me3) is associated with promoters of active genes and found at hot spots for DNA recombination. Here we have shown that PAXIP1 (also known as PTIP), a protein associated with MLL3 and MLL4 methyltransferase and the DN ... Full text Link to item Cite

Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub.

Journal Article Proc Natl Acad Sci U S A · December 11, 2012 Featured Publication Antigen receptor locus V(D)J recombination requires interactions between widely separated variable (V), diversity (D), and joining (J) gene segments, but the mechanisms that generate these interactions are not well understood. Here we assessed mechanisms t ... Full text Link to item Cite

Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement.

Journal Article Trends Immunol · April 2012 Featured Publication The somatic recombination of lymphocyte antigen receptor loci is integral to lymphocyte differentiation and adaptive immunity. Here we review the relation of this highly choreographed process with the zinc finger protein CTCF and with cohesin, a protein co ... Full text Link to item Cite

Regulation of TCRβ allelic exclusion by gene segment proximity and accessibility.

Journal Article J Immunol · December 15, 2011 Featured Publication Ag receptor loci are regulated to promote allelic exclusion, but the mechanisms are not well understood. Assembly of a functional TCR β-chain gene triggers feedback inhibition of V(β)-to-DJ(β) recombination in double-positive (DP) thymocytes, which correla ... Full text Link to item Cite

Long-distance regulation of fetal V(δ) gene segment TRDV4 by the Tcrd enhancer.

Journal Article J Immunol · September 1, 2011 Featured Publication Murine Tcra and Tcrd gene segments are organized into a single genetic locus (Tcra/Tcrd locus) that undergoes V(D)J recombination in CD4(-)CD8(-) double-negative (DN) thymocytes to assemble Tcrd genes and in CD4(+)CD8(+) double-positive thymocytes to assem ... Full text Link to item Cite

A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation.

Journal Article Nature · August 10, 2011 Featured Publication Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis. There is growing evidence that cohesin also forms long-range chromosomal cis-interaction ... Full text Link to item Cite

Immunology at Duke: 2011.

Journal Article Immunol Res · April 2011 Featured Publication Full text Link to item Cite

Orchestrating T-cell receptor α gene assembly through changes in chromatin structure and organization.

Journal Article Immunol Res · April 2011 Featured Publication V(D)J recombination is regulated through changes in chromatin structure that allow recombinase proteins access to recombination signal sequences and through changes in three-dimensional chromatin organization that bring pairs of distant recombination signa ... Full text Link to item Cite

A barrier-type insulator forms a boundary between active and inactive chromatin at the murine TCRβ locus.

Journal Article J Immunol · March 15, 2011 Featured Publication In CD4(-)CD8(-) double-negative thymocytes, the murine Tcrb locus is composed of alternating blocks of active and inactive chromatin containing Tcrb gene segments and trypsinogen genes, respectively. Although chromatin structure is appreciated to be critic ... Full text Link to item Cite

Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination.

Journal Article J Exp Med · December 20, 2010 Featured Publication V(D)J recombination assembles antigen receptor genes in a well-defined order during lymphocyte development. This sequential process has long been understood in the context of the accessibility model, which states that V(D)J recombination is regulated by co ... Full text Link to item Cite

Distinct contracted conformations of the Tcra/Tcrd locus during Tcra and Tcrd recombination.

Journal Article J Exp Med · August 30, 2010 Featured Publication Studies have suggested that antigen receptor loci adopt contracted conformations to promote long-distance interactions between gene segments during V(D)J recombination. The Tcra/Tcrd locus is unique because it undergoes highly divergent Tcrd and Tcra recom ... Full text Link to item Cite

Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo.

Journal Article J Immunol · June 15, 2010 Featured Publication Accessibility of chromosomal recombination signal sequences to the RAG protein complex is known to be essential for V(D)J recombination at Ag receptor loci in vivo. Previous studies have addressed the roles of cis-acting regulatory elements and germline tr ... Full text Link to item Cite

CD69 gene is differentially regulated in T and B cells by evolutionarily conserved promoter-distal elements.

Journal Article J Immunol · November 15, 2009 CD69 is a type II C-type lectin involved in lymphocyte migration and cytokine secretion. CD69 expression represents one of the earliest available indicators of leukocyte activation and its rapid induction occurs through transcriptional activation. In this ... Full text Link to item Cite

Mechanics of T cell receptor gene rearrangement.

Journal Article Curr Opin Immunol · April 2009 The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination sign ... Full text Link to item Cite

Germline transcription: a key regulator of accessibility and recombination.

Journal Article Adv Exp Med Biol · 2009 The developmental control of V(D)J recombination is imposed at the level of chromatin accessibility of recombination signal sequences (RSSs) to the recombinase machinery. Cis-acting transcriptional regulatory elements such as promoters and enhancers play a ... Full text Link to item Cite

Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments.

Journal Article Nat Immunol · July 2008 Studies of antigen-receptor loci have linked directed monoallelic association with pericentromeric heterochromatin to the initiation or maintenance of allelic exclusion. Here we provide evidence for a fundamentally different basis for T cell antigen recept ... Full text Link to item Cite

Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination.

Journal Article EMBO J · October 17, 2007 The T early alpha (TEA) promoter in the murine Tcra locus generates noncoding transcripts that extend across the 65 kb Jalpha array. Here, we have analyzed the significance of TEA transcription for Tcra locus regulation through the targeted introduction of ... Full text Link to item Cite

Multiple constraints at the level of TCRalpha rearrangement impact Valpha14i NKT cell development.

Journal Article J Immunol · August 15, 2007 CD1d-restricted NKT cells that express an invariant Valpha14 TCR represent a subset of T cells implicated in the regulation of several immune responses, including autoimmunity, infectious disease, and cancer. Proper rearrangement of Valpha14 with the Jalph ... Full text Link to item Cite

T cell development: better living through chromatin.

Journal Article Nat Immunol · July 2007 T lymphocyte development is directed by a gene-expression program that occurs in the complex nucleoprotein environment of chromatin. This review examines basic principles of chromatin regulation and evaluates ongoing progress toward understanding how the c ... Full text Link to item Cite

T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.

Journal Article Blood · April 15, 2007 CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodefi ... Full text Link to item Cite

Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination.

Journal Article Proc Natl Acad Sci U S A · January 16, 2007 During the recombination of variable (V) and joining (J) gene segments at the T cell receptor alpha locus, a ValphaJalpha joint resulting from primary rearrangement can be replaced by subsequent rounds of secondary rearrangement that use progressively more ... Full text Link to item Cite

Regulation of T cell receptor-alpha gene recombination by transcription.

Journal Article Nat Immunol · October 2006 Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through ... Full text Link to item Cite

A role for MAPK in feedback inhibition of Tcrb recombination.

Journal Article J Immunol · June 1, 2006 The Tcrb locus is subject to a host of regulatory mechanisms that impart a strict cell and developmental stage-specific order to variable (V), diversity (D), and joining (J) gene segment recombination. The Tcrb locus is also regulated by allelic exclusion ... Full text Link to item Cite

Some nuts are tougher to crack than others.

Journal Article Immunity · April 2006 In this issue of Immunity, Oestreich et al. (2006) show that, during V(D)J recombination, RSSs may have distinct accessibility requirements. Some rely on an enhancer-intrinsic, general chromatin opening function, whereas others require enhancer-promoter in ... Full text Link to item Cite

Turning T-cell receptor beta recombination on and off: more questions than answers.

Journal Article Immunol Rev · February 2006 Successful V(D)J recombination at the T-cell receptor beta (Tcrb) locus is critical for early thymocyte development. The locus is subject to a host of regulatory mechanisms that impart a strict developmental order to Tcrb recombination events and that insu ... Full text Link to item Cite

Allele-specific regulation of TCR beta variable gene segment chromatin structure.

Journal Article J Immunol · October 15, 2005 Allelic exclusion of the murine Tcrb locus is imposed at the level of recombination and restricts each cell to produce one functional VDJbeta rearrangement. Allelic exclusion is achieved through asynchronous Vbeta to DJbeta recombination as well as feedbac ... Full text Link to item Cite

Regulation of TCR delta and alpha repertoires by local and long-distance control of variable gene segment chromatin structure.

Journal Article J Exp Med · August 15, 2005 Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4- CD8- (double negative [DN]) and CD4+ CD8+ (double positive [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex re ... Full text Link to item Cite

Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters.

Journal Article Nat Immunol · May 2005 Assembly of the gene encoding T cell receptor alpha (Tcra) is characterized by an orderly progression of primary and secondary V(alpha)-to-J(alpha) recombination events across the J(alpha) array, but the targeting mechanisms responsible for this progressio ... Full text Link to item Cite

Regulation of the murine Ddelta2 promoter by upstream stimulatory factor 1, Runx1, and c-Myb.

Journal Article J Immunol · April 1, 2005 Accessibility control of V(D)J recombination at Ag receptor loci depends on the coordinate activities of transcriptional enhancers and germline promoters. Recombination of murine Tcrd gene segments is known to be regulated, at least in part, by the Tcrd en ... Full text Link to item Cite

Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility.

Journal Article Nat Immunol · February 2005 Allelic exclusion of V(beta)-to-DJ(beta) recombination depends on asynchronous rearrangement of alleles of the gene encoding T cell receptor beta in double-negative thymocytes and feedback inhibition that is maintained in double-positive thymocytes. Feedba ... Full text Link to item Cite

Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer.

Journal Article J Immunol · October 15, 2004 The TCR delta enhancer (Edelta) and TCR alpha enhancer (Ealpha) play critical roles in the temporal and lineage-specific control of V(D)J recombination and transcription at the TCR alphadelta locus, working as a developmental switch controlling a transitio ... Full text Link to item Cite

Enforcing order within a complex locus: current perspectives on the control of V(D)J recombination at the murine T-cell receptor alpha/delta locus.

Journal Article Immunol Rev · August 2004 V(D)J recombination proceeds according to defined developmental programs at T-cell receptor (TCR) and immunoglobulin loci as a function of cell lineage and stage of differentiation. Although the molecular details are still lacking, such regulation is thoug ... Full text Link to item Cite

Targeted inhibition of V(D)J recombination by a histone methyltransferase.

Journal Article Nat Immunol · March 2004 The tissue- and stage-specific assembly of antigen receptor genes by V(D)J recombination is regulated by changes in the chromatin accessibility of target gene segments. This dynamic remodeling process is coordinated by cis-acting promoters and enhancers, w ... Full text Link to item Cite

Allelic Exclusion, Isotypic Exclusion, and the Developmental Regulation of V(D)J Recombination

Chapter · January 1, 2004 This chapter focuses on the various mechanisms that impart developmental control to V(D)J recombination and that yield allelically and isotypically excluded antigen receptor repertoires. The lymphoid specificity of V(D)J recombination reflects the regulate ... Full text Cite

Gene segment selection in V(D)J recombination: accessibility and beyond.

Journal Article Nat Immunol · July 2003 V(D)J recombination assembles genes encoding antigen receptors according to defined developmental programs in immature B and T lymphocytes. The 'accessibility hypothesis' was initially invoked to explain how a single recombinase complex could control the l ... Full text Link to item Cite

Distinct roles for c-Myb and core binding factor/polyoma enhancer-binding protein 2 in the assembly and function of a multiprotein complex on the TCR delta enhancer in vivo.

Journal Article J Immunol · October 15, 2002 Enhancers and promoters within TCR loci functionally collaborate to modify chromatin structure and to confer accessibility to the transcription and V(D)J recombination machineries during T cell development in the thymus. Two enhancers at the TCRalphadelta ... Full text Link to item Cite

Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility.

Journal Article Proc Natl Acad Sci U S A · September 17, 2002 Antigen receptor gene assembly is regulated by transcriptional promoters and enhancers, which control the accessibility of gene segments to a lymphocyte-specific V(D)J recombinase. However, it remained unclear whether accessibility depends on the process o ... Full text Link to item Cite

Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

Journal Article Nat Immunol · May 2002 T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L) ... Full text Link to item Cite

A change in the structure of Vbeta chromatin associated with TCR beta allelic exclusion.

Journal Article J Immunol · March 1, 2002 To investigate chromatin control of TCR beta rearrangement and allelic exclusion, we analyzed TCR beta chromatin structure in double negative (DN) thymocytes, which are permissive for TCR beta recombination, and in double positive (DP) thymocytes, which ar ... Full text Link to item Cite

Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus.

Journal Article Immunology · September 2001 Although situated close together within the T-cell receptor (TCR) alpha/delta locus, TCR delta and TCR alpha gene segments are controlled by two developmental stage-specific enhancers and are activated according to distinct developmental programmes. We pre ... Full text Link to item Cite

V(D)J recombination becomes accessible.

Journal Article J Exp Med · April 2, 2001 Full text Link to item Cite

Chemokines have diverse abilities to form solid phase gradients.

Journal Article Clin Immunol · April 2001 Chemokines play critical roles in leukocyte recruitment into sites of inflammation such as rheumatoid arthritis (RA). While chemokines immobilized on endothelium (solid-phase), but not soluble chemokines, direct rolling leukocytes to firmly adhere to endot ... Full text Link to item Cite

Chemokine production by G protein-coupled receptor activation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT.

Journal Article J Immunol · December 15, 2000 Chemoattractants are thought to be the first mediators generated at sites of bacterial infection. We hypothesized that signaling through G protein-coupled chemoattractant receptors may stimulate cytokine production. To test this hypothesis, a human mast ce ... Full text Link to item Cite

T cell receptor-dependent activation of human lymphocytes through cell surface ganglioside GT1b: implications for innate immunity.

Journal Article Eur J Immunol · November 2000 Gangliosides form a component of the glycosphingolipid-rich membrane microdomains recently shown to play an important role in receptor signal transduction. Specific gangliosides also serve as receptors for binding and internalization of bacterial toxins. I ... Full text Link to item Cite

A role for histone acetylation in the developmental regulation of VDJ recombination.

Journal Article Science · January 21, 2000 VDJ recombination is developmentally regulated in vivo by enhancer-dependent changes in the accessibility of chromosomal recombination signal sequences to the recombinase, but the molecular nature of these changes is unknown. Here histone H3 acetylation wa ... Full text Link to item Cite

Accessibility control of T cell receptor gene rearrangement in developing thymocytes. The TCR alpha/delta locus.

Journal Article Immunol Res · 2000 The joining of T cell receptor (TCR) and immunoglobulin (Ig) gene segments through the process of V(D)J recombination occurs in a lineage-specific and developmental-stage-specific way during the early stages of lymphocyte development. Such developmental re ... Full text Link to item Cite

Flanking nuclear matrix attachment regions synergize with the T cell receptor delta enhancer to promote V(D)J recombination.

Journal Article Proc Natl Acad Sci U S A · October 12, 1999 Previous studies have identified nuclear matrix attachment regions (MARs) that are closely associated with transcriptional enhancers in the IgH, Igkappa, and T cell receptor (TCR) beta loci, but have yielded conflicting information regarding their function ... Full text Link to item Cite

Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta.

Journal Article J Immunol · August 15, 1999 The ability of chemokines to bind to glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix is thought to play a crucial role in chemokine function. We investigated the structural basis for chemokine binding to GAGs by using in vitro mu ... Link to item Cite

Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes.

Journal Article J Immunol · July 1, 1999 Although tightly linked, the TCR alpha and delta genes are expressed specifically in T lymphocytes, whereas the Dad1 gene is ubiquitously expressed. Between TCR alpha and Dad1 are eight DNase I hypersensitive sites (HS). HS1 colocalizes with the TCR alpha ... Link to item Cite

A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation.

Journal Article Immunity · June 1999 V(D)J recombination and transcription within the TCR alpha/delta locus are regulated by three characterized cis-acting elements: the TCR delta enhancer (Edelta), TCR alpha enhancer (Ealpha), and T early alpha (TEA) promoter. Analysis of enhancer and promot ... Full text Link to item Cite

Regulation of chromatin accessibility for V(D)J recombination.

Journal Article Cold Spring Harb Symp Quant Biol · 1999 Full text Link to item Cite

Developmental regulation of V(D)J recombination at the TCR alpha/delta locus.

Journal Article Immunol Rev · October 1998 The T-cell receptor (TCR) alpha/delta locus includes a large number of V, D, J and C gene segments that are used to produce functional TCR delta and TCR alpha chains expressed by distinct subsets of T lymphocytes. V(D)J recombination events within the locu ... Full text Link to item Cite

Cooperation among multiple transcription factors is required for access to minimal T-cell receptor alpha-enhancer chromatin in vivo.

Journal Article Mol Cell Biol · June 1998 To understand the molecular basis for the dramatic functional synergy between transcription factors that bind to the minimal T-cell receptor alpha enhancer (Ealpha), we analyzed enhancer occupancy in thymocytes of transgenic mice in vivo by genomic footpri ... Full text Link to item Cite

Enhancer control of local accessibility to V(D)J recombinase.

Journal Article Mol Cell Biol · August 1997 We have studied the role of transcriptional enhancers in providing recombination signal sequence (RSS) accessibility to V(D)J recombinase by examining mice carrying a transgenic human T-cell receptor (TCR) delta gene minilocus. This transgene is composed o ... Full text Link to item Cite

An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus.

Journal Article Proc Natl Acad Sci U S A · May 13, 1997 T cell receptor (TCR) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development. An enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was localized to a 2.0-kb ... Full text Link to item Cite

Identification of a glycosaminoglycan-binding site in chemokine macrophage inflammatory protein-1alpha.

Journal Article J Biol Chem · April 11, 1997 Chemokines bind to receptors of the seven-transmembrane type on target cells and also bind to glycosaminoglycans (GAGs), including heparin. In this study, we have sought to identify structural motifs mediating binding of the beta-chemokine macrophage infla ... Full text Link to item Cite

Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2.

Journal Article J Exp Med · April 7, 1997 We have analyzed transgenic mice carrying versions of a human T cell receptor (TCR)-delta gene minilocus to study the developmental control of VDJ (variable/diversity/joining) recombination. Previous data indicated that a 1.4-kb DNA fragment carrying the T ... Full text Link to item Cite

Regulation of I-309 gene expression in human monocytes by endogenous interleukin-1.

Journal Article Eur J Immunol · March 1997 Activated human monocytes are a source of numerous beta-chemokines. The present study was conducted to determine whether these cells produce the human beta-chemokine I-309 and to compare the induction requirements of I-309 to those of other beta-chemokines ... Full text Link to item Cite

Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer.

Journal Article J Exp Med · January 6, 1997 The role of T cell receptor alpha enhancer (E alpha) cis-acting elements in the developmental regulation of VDJ recombination at the TCR alpha/delta locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We de ... Full text Link to item Cite

Regulation of T cell receptor delta gene rearrangement by c-Myb.

Journal Article J Exp Med · January 1, 1996 Developmental activation of VDJ recombination at the T cell receptor (TCR) delta locus is controlled by an intronic transcriptional enhancer (E delta). Transcriptional activation by E delta is dependent on c-Myb. To determine whether c-Myb plays a role in ... Full text Link to item Cite

Transcriptional regulation of the human T cell receptor delta gene.

Journal Article Immunobiology · July 1995 T cell receptor delta gene expression is regulated by a T cell-specific transcriptional enhancer located within the J delta 3-C delta intron. An essential element of the enhancer was localized to a small 30 bp segment denoted delta E3. Two specific factors ... Full text Link to item Cite

c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor delta enhancer.

Journal Article Mol Cell Biol · June 1995 A T-cell-specific transcriptional enhancer lies within the J delta 3-C delta intron of the human T-cell receptor delta gene. We have previously shown that a 30-bp element, denoted delta E3, acts as the minimal TCR delta enhancer and that within delta E3, a ... Full text Link to item Cite

The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations.

Journal Article J Immunol · September 15, 1994 The chemokines are a family of immune mediators involved in a wide range of inflammatory processes, most importantly as chemoattractants of monocytes, neutrophils, lymphocytes, and fibroblasts to sites of inflammation. Nuclear magnetic resonance and x-ray ... Link to item Cite

Immunochemical and molecular analysis of antigen binding to lipid anchored and soluble forms of an MHC independent human alpha/beta T cell receptor.

Journal Article Mol Immunol · August 1994 We have constructed antigen-specific chimeric human T cell receptor (TCR) molecules deleted of the transmembrane domain and containing the signal sequence for the biosynthesis of the phosphatidyl inositol glycan (GPI) linkage. These membrane-anchored forms ... Full text Link to item Cite

Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers.

Journal Article J Exp Med · June 1, 1994 To analyze the regulation of gene rearrangement at the T cell receptor (TCR) alpha/delta locus during T cell development, we generated transgenic mice carrying a human TCR delta gene minilocus. We previously showed that the presence of the TCR delta enhanc ... Full text Link to item Cite

Expression of multiple chemokine genes by a human mast cell leukemia.

Journal Article J Biol Chem · May 13, 1994 The chemokines are a large group of cytokines that are recognized to be important mediators of inflammation. In this study we show that the human mast cell leukemia line HMC-1 is a source of multiple chemokines, including I-309, monocyte chemoattractant pr ... Link to item Cite

Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor delta transgene.

Journal Article J Exp Med · January 1, 1994 The rearrangement and expression of T cell receptor (TCR) gene segments occurs in a highly ordered fashion during thymic ontogeny of T lymphocytes. To study the regulation of gene rearrangement within the TCR alpha/delta locus, we generated transgenic mice ... Full text Link to item Cite

Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors.

Journal Article Mol Cell Biol · January 1994 A T-cell-specific transcriptional enhancer lies within the J delta 3-C delta intron of the human T-cell receptor (TCR) delta gene. The 30-bp minimal enhancer element denoted delta E3 carries a core sequence (TGTGGTTT) that binds a T-cell-specific factor, a ... Full text Link to item Cite

Indistinguishable nuclear factor binding to functional core sites of the T-cell receptor delta and murine leukemia virus enhancers.

Journal Article Mol Cell Biol · November 1992 We have previously shown that the delta E3 site is an essential element for transcriptional activation by the human T-cell receptor (TCR) delta enhancer and identified two factors, NF-delta E3A and NF-delta E3C, that bound to overlapping core (TGTGGTTT) an ... Full text Link to item Cite

The human cytokine I-309 is a monocyte chemoattractant.

Journal Article Proc Natl Acad Sci U S A · April 1, 1992 The human cytokine I-309 is a small glycoprotein secreted by activated T lymphocytes and structurally related to a number of inflammatory cytokines. To investigate the biological activities of I-309 protein, we produced a stable Chinese hamster ovary cell ... Full text Link to item Cite

Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines.

Journal Article Crit Rev Immunol · 1992 Studies conducted in many laboratories over the past several years have resulted in the identification and initial characterization of a large superfamily of structurally and functionally related inflammatory cytokines. This superfamily currently includes ... Link to item Cite

Identification of an essential site for transcriptional activation within the human T-cell receptor delta enhancer.

Journal Article Mol Cell Biol · November 1991 A T-cell-specific transcriptional enhancer was previously identified within the J delta 3-C delta intron of the human T-cell receptor (TCR) delta gene, and seven distinct binding sites for nuclear factors (delta E1 to delta E7) were defined by DNase I foot ... Full text Link to item Cite

Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines.

Journal Article J Immunol · October 15, 1990 We previously reported the isolation and characterization of a cDNA clone, I-309, that encodes a small secreted protein produced by activated human T lymphocytes. This protein is structurally related to a large number of recently identified proteins that a ... Link to item Cite

A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production.

Journal Article J Exp Med · September 1, 1990 The rearrangement and expression of human T cell receptor (TCR)-gamma and -delta gene segments in clonal and polyclonal populations of early fetal and postnatal human TCR-gamma/delta thymocytes were examined. The data suggest that the TCR-gamma and -delta ... Full text Link to item Cite

A T cell-specific transcriptional enhancer within the human T cell receptor delta locus.

Journal Article Science · March 9, 1990 The T cell antigen receptor (TCR) delta gene is located within the TCR alpha locus. A T cell-specific transcriptional enhancer, distinct from the TCR alpha enhancer, has been identified within the J delta 3-C delta intron of the human T cell receptor delta ... Full text Link to item Cite

Human T cell receptor-gamma and -delta chain pairing analyzed by transfection of a T cell receptor-delta negative mutant cell line.

Journal Article J Immunol · February 1, 1990 Specific TCR V gamma and V delta segments are found to be coordinately used on subpopulations of gamma delta T lymphocytes. The reasons for this phenomenon are unknown, but may include the inability of particular chains expressing unique V delta and V gamm ... Link to item Cite

A novel polypeptide secreted by activated human T lymphocytes.

Journal Article J Immunol · November 1, 1989 We have identified two cDNA clones, I-309 and G-26, which define genes expressed abundantly in activated human PBMC, but at low or undetectable levels in resting PBMC. Based upon nucleotide sequence analysis, both clones are predicted to encode small, stru ... Link to item Cite

Expression of human T cell receptor-gamma delta structural forms.

Journal Article J Immunol · May 15, 1989 The human TCR-gamma delta occurs in three biochemically distinct forms (forms 1, 2bc, and 2abc). A 40-kDa TCR gamma-chain is disulfide-linked to the TCR delta-chain in form 1, whereas 40-kDa or 55-kDa TCR-gamma polypeptides are noncovalently associated wit ... Link to item Cite

Diversity and organization of human T cell receptor delta variable gene segments.

Journal Article J Exp Med · January 1, 1989 Previous studies of the human TCR-delta gene identified a single commonly used V delta segment, denoted V delta 1. To better understand the extent of the human TCR-delta V gene repertoire, TCR-delta transcripts and gene rearrangements were examined in a ne ... Full text Link to item Cite

Human T cell receptor gamma delta structure.

Journal Article Adv Exp Med Biol · 1989 Link to item Cite

Genomic organization of the human T-cell antigen-receptor alpha/delta locus.

Journal Article Proc Natl Acad Sci U S A · November 1988 Two clusters of overlapping cosmid clones comprising about 100 kilobases (kb) at the human T-cell antigen-receptor alpha/delta locus were isolated from a genomic library. The structure of the germ-line V delta 1 variable gene segment was determined. V delt ... Full text Link to item Cite

Extensive junctional diversity of rearranged human T cell receptor delta genes.

Journal Article Science · June 10, 1988 The human T cell receptor delta (TCR delta) gene encodes one component of the TCR gamma delta-CD3 complex found on subsets of peripheral blood and thymic T cells. Human TCR delta diversity was estimated by characterizing rearrangements in TCR gamma delta c ... Full text Link to item Cite

The gamma delta T cell receptor.

Journal Article Adv Immunol · 1988 Link to item Cite

The γδT Cell Receptor

Journal Article Advances in Immunology · January 1, 1988 Along with important conceptual similarities, there are also fundamental differences in structure and in the mode of operation of the antigen receptors on B and T cells. The B lymphocyte receptor is the immunoglobulin molecule. The large number of antibody ... Full text Cite

Identification of putative human T cell receptor delta complementary DNA clones.

Journal Article Science · October 30, 1987 A novel T cell receptor (TCR) subunit termed TCR delta, associated with TCR gamma and CD3 polypeptides, was recently found on a subpopulation of human T lymphocytes. T cell-specific complementary DNA clones present in a human TCR gamma delta T cell complem ... Full text Link to item Cite

Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit.

Journal Article Science · October 30, 1987 The T cell receptor (TCR) delta protein is expressed as part of a heterodimer with TCR gamma, in association with the CD3 polypeptides on a subset of functional peripheral blood T lymphocytes, thymocytes, and certain leukemic T cell lines. A monoclonal ant ... Full text Link to item Cite

T-cell receptors of human suppressor cells.

Journal Article Nature · October 8, 1987 Cells which can suppress the immune response to an antigen (TS cells) appear to be essential for regulation of the immune system. But the characterization of the TS lineage has not been extensive and many are sceptical of studies using uncloned or hybrid T ... Full text Link to item Cite

Two forms of HLA class I molecules in human plasma.

Journal Article Hum Immunol · October 1987 Soluble HLA-A,-B antigens have previously been detected in human plasma. More recently, these molecules have been demonstrated to be secreted in water soluble form by cell lines and peripheral blood lymphocytes in vitro due to RNA splicing events which del ... Full text Link to item Cite

Structurally divergent human T cell receptor gamma proteins encoded by distinct C gamma genes.

Journal Article Science · July 3, 1987 The human T cell receptor (TCR) gamma polypeptide occurs in structurally distinct forms on certain peripheral blood T lymphocytes. Complementary DNA clones representing the transcripts of functionally rearranged TCR gamma genes in these cells have been ana ... Full text Link to item Cite

T3 glycoprotein is functional although structurally distinct on human T-cell receptor gamma T lymphocytes.

Journal Article Proc Natl Acad Sci U S A · June 1987 The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocyte ... Full text Link to item Cite

Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation.

Journal Article J Exp Med · April 1, 1987 An assay has been developed to assess the dynamics of cell surface glycoproteins, in which neuraminidase digestion of intact cells is used to determine the fate of cell surface molecules initially labelled via lactoperoxidase-catalyzed iodination. This app ... Full text Link to item Cite

Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes.

Journal Article Nature · February 19, 1987 The T-cell receptor (TCR) gamma polypeptide is expressed associated with CD3 (T3) on the surface of normal human peripheral blood lymphocytes. These cells function as non-MHC-restricted cytotoxic T lymphocytes (CTL)and thus may play an important role in ho ... Full text Link to item Cite

Identification of a putative second T-cell receptor.

Journal Article Nature · July 10, 1986 Framework monoclonal antibodies have identified a population of human lymphocytes that express the T3 glycoprotein but not the T-cell receptor (TCR) alpha- and beta-subunits. Chemical crosslinking experiments reveal that these lymphocytes express novel T3- ... Full text Link to item Cite

Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway.

Journal Article J Exp Med · May 1, 1986 Human class I major histocompatibility antigens (HLA-A, -B and -C) are integral membrane protein heterodimers, which are anchored in the membrane via a stretch of hydrophobic amino acids near the carboxyl terminus of the heavy chain. It has previously been ... Full text Link to item Cite

Structural analysis of the functional sites of class I HLA antigens.

Journal Article Immunol Rev · July 1985 Considerable knowledge of the molecular organization of class I HLA antigens has been attained through extensive structural analysis of these proteins and their genes. Particularly, the nature and location of the polymorphic regions has been established, a ... Full text Link to item Cite

Unusual RNA splicing generates a secreted form of HLA-A2 in a mutagenized B lymphoblastoid cell line.

Journal Article EMBO J · May 1985 Human class I major histocompatibility antigens (HLA-A, -B and -C) are integral membrane glycoprotein heterodimers. A mutagenized B lymphoblastoid cell line has been previously shown to synthesize two forms of the HLA-A2 antigen; a minor form which remains ... Full text Link to item Cite

Structural analysis of an HLA-B7 antigen variant detected by cytotoxic T lymphocytes.

Journal Article J Immunol · August 1984 It has been demonstrated previously that lymphocytes of donor CF (HLA-A29,w33; B7,14) are not recognized by the HLA-B7-specific CTL clone HG-31. This report presents a structural comparison of the HLA-B7 antigen of donor CF with a "normal" HLA-B7 antigen, ... Link to item Cite

Cysteines in the transmembrane region of major histocompatibility complex antigens are fatty acylated via thioester bonds.

Journal Article J Biol Chem · June 10, 1984 Exogenous radioactive palmitic acid is incorporated post-translationally into the HLA-B and -DR heavy chains, but not HLA-A heavy chains or -DR light chains of the human B lymphoblastoid cells JY and T51 . Protease digestions localize the label to the tran ... Link to item Cite

Characterization of a B lymphoblastoid cell line mutant that secretes HLA-A2.

Journal Article J Immunol · June 1984 HLA-A2 antigen mutants were obtained previously from the B lymphoblastoid cell line T5-1 by mutagenesis followed by immunoselection. Here we present biochemical studies of one particular mutant, clone 8.14.1. These cells synthesize two forms of HLA-A2: a m ... Link to item Cite

Structural analysis of HLA-A2 antigen from immunoselected mutant 8.6.1: further definition of an HLA-A2-specific serological determinant.

Journal Article J Immunol · December 1983 The HLA-A2 mutant cell line 8.6.1 was isolated previously from the lymphoblastoid B cell line T5-1 (HLA-A1, -A2, -B8, and -B27) by immunoselection with the mouse HLA-A2-specific monoclonal antibody BB7.2 and complement. The HLA-A2 molecules synthesized by ... Link to item Cite

Recognition of HLA-A2 mutant and variant target cells by an HLA-A2 allospecific human cytotoxic T lymphocyte line.

Journal Article J Immunol · September 1983 HLA-A2 specific human cytotoxic T lymphocytes (CTL) cell lines have been developed using T cell growth factor and coculture of peripheral blood lymphocytes with selected allogeneic target cell lines. The CTL-8 line showed specificity for human leukocyte an ... Link to item Cite

Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes. II. Variant DK1: evidence for a discrete CTL recognition region.

Journal Article J Immunol · April 1983 Multiple amino acid sequence differences distinguish individual HLA antigens. Those residues important in immune recognition events have not been defined. Recent studies have identified HLA-A2 structural variants that, although serologically indistinguisha ... Link to item Cite

HLA-A2 mutants immunoselected in vitro. Definition of residues contributing to an HLA-A2-specific serological determinant.

Journal Article J Exp Med · January 1, 1983 The HLA-A2-specific mouse monoclonal antibody BB7.2 plus complement has been used to immunoselect variant clones of the lymphoblastoid cell line T5-1 (HLA-A1, -A2, -B8, and -B27). Members of one class of variant clones appear to express cell surface HLA-A2 ... Full text Link to item Cite

HLA antigen structural gene mutants selected with an allospecific monoclonal antibody.

Journal Article Proc Natl Acad Sci U S A · December 1982 The HLA-A2 antigen-specific monoclonal antibody BB7.2 and complement were used to immunoselect mutants from an ethyl methanesulfonate-mutagenized human B lymphoid cell line, T5-1. Surviving colonies were screened by radioimmune binding with BB7.2 and with ... Full text Link to item Cite

Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes: variants M7 and DR1.

Journal Article Biochemistry · November 23, 1982 Comparative primary structural analyses have begun to elucidate polymorphic residues and segments of the class I antigens of the major histocompatibility complex, at least some of which presumably contribute to determinants important in immune recognition ... Full text Link to item Cite

Delineation of immunologically and biochemically distinct HLA-A2 antigens.

Journal Article J Immunol · August 1982 Cytotoxic T cell (CTL) recognition of influenza virus in conjunction with HLA-A2 was examined in a population study. Virus-infected target cells from three unrelated A2-positive donors were not lysed by virus-immune CTL from any donor matched only for A2. ... Link to item Cite

Human histocompatibility antigen mutants immunoselected in vitro. Biochemical analysis of a mutant which synthesizes an altered HLA-A2 heavy chain.

Journal Article J Biol Chem · May 10, 1982 Immunoselection with HLA-A2 or HLA-A1 specific alloantisera has been utilized to isolate spontaneously arising and mutagen-induced variants from the B lymphoblastoid cell line T5-1 (HLA haplotypes DR3, B8, A1 and DR1, B27, Cw1, A2). Such variants are chara ... Link to item Cite

Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules.

Journal Article Hum Immunol · October 1980 The self-specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to identify the relationship between the self-determinants which they recognize and the serologically defined HLA-A and -B antigenic determinants. Virus-immun ... Full text Link to item Cite

Assembly and maturation of HLA-A and HLA-B antigens in vivo.

Journal Article Cell · December 1979 HLA-A and HLA-B antigens are integral membrane glycoproteins which consist of a glycosylated heavy chain embedded in the membrane in noncovalent association with beta 2-microglobulin, a water-soluble polypeptide. The assembly and maturation of these antige ... Full text Link to item Cite