Michael S. Krangel
George Barth Geller Distinguished Professor of Immunology
The process of V(D)J recombination assembles T cell receptor (TCR) genes (α,β,γ,δ) from variable (V), diversity (D) and joining (J) gene segments during T cell development, and is essential for the formation of diverse antigen receptor repertoires on αβ and γδ T lymphocytes. We are interested in the molecular basis for developmentally regulated rearrangement and expression of murine TCR genes. One focus of our studies is the TCRα/δ locus, because it represents an intriguing model with two sets of gene segments that are differentially activated for recombination during T cell development. We are also studying the TCRβ locus, because this locus presents a model in which there is a developmental inactivation of V(D)J recombination associated with the process of allelic exclusion. V(D)J recombination depends on the ability of recombinase proteins RAG1 and RAG2 to recognize and generate double-strand breaks at recombination signal sequences that flank TCR gene segments. Our main focus has been on the role of chromatin structure in defining the portions of these loci that are accessible to the RAG recombinase and therefore active for V(D)J recombination, and on the mechanisms by which cis-regulatory elements within these loci (enhancers, promoters) function as developmental regulators of chromatin structure. Our primary approach has been to manipulate cis-acting elements within these loci by gene targeting, and to study the effects of these manipulations on locus chromatin structure and recombination events in developing thymocytes in vivo. An important outcome of this work has been our demonstration that enhancer- and promoter-directed transcription through recombination signal sequences can displace and covalently modify nucleosomes to provide accessibility for RAG binding and V(D)J recombination.
Recent work in our laboratory and elsewhere has highlighted additional properties of antigen receptor loci that likely to play important roles in developmental regulation. One area of interest is subnuclear positioning. We have used three-dimensional fluorescence in situ hybridization (3D-FISH) to show that TCRβ alleles interact stochastically and at high frequency with the nuclear lamina and with foci of pericentromeric heterochromatin, and that these interactions are inhibitory to V(D)J recombination. We suspect that these inhibitory interactions help to promote allelic exclusion by diminishing the likelihood of simultaneous V to DJ recombination on both alleles. Current work is aimed at developing a better understanding of how the TCRβ locus interacts with the nuclear lamina and the mechanism by which this interaction impacts recombination events.
A second area of interest is locus conformation. It is now appreciated that recombination events at antigen receptor loci depend on locus conformational changes that bring into proximity gene segments that may be widely separated in the linear DNA sequence. Conformational states can be defined using 3D-FISH or a chemical crosslinking approach called chromosome conformation capture (3C). Recent studies indicate that developmental changes in locus conformation contribute to allelic exclusion at the TCRβ locus and mediate a transition from TCRδ to TCRα rearrangement at the TCRα/δ locus. Current work aims to address at a molecular level how locus conformational states are maintained and modified during T cell development and how these changes impact long-distance transactions including enhancer-promoter communication and V(D)J recombination.
Recent work in our laboratory and elsewhere has highlighted additional properties of antigen receptor loci that likely to play important roles in developmental regulation. One area of interest is subnuclear positioning. We have used three-dimensional fluorescence in situ hybridization (3D-FISH) to show that TCRβ alleles interact stochastically and at high frequency with the nuclear lamina and with foci of pericentromeric heterochromatin, and that these interactions are inhibitory to V(D)J recombination. We suspect that these inhibitory interactions help to promote allelic exclusion by diminishing the likelihood of simultaneous V to DJ recombination on both alleles. Current work is aimed at developing a better understanding of how the TCRβ locus interacts with the nuclear lamina and the mechanism by which this interaction impacts recombination events.
A second area of interest is locus conformation. It is now appreciated that recombination events at antigen receptor loci depend on locus conformational changes that bring into proximity gene segments that may be widely separated in the linear DNA sequence. Conformational states can be defined using 3D-FISH or a chemical crosslinking approach called chromosome conformation capture (3C). Recent studies indicate that developmental changes in locus conformation contribute to allelic exclusion at the TCRβ locus and mediate a transition from TCRδ to TCRα rearrangement at the TCRα/δ locus. Current work aims to address at a molecular level how locus conformational states are maintained and modified during T cell development and how these changes impact long-distance transactions including enhancer-promoter communication and V(D)J recombination.
Current Appointments & Affiliations
- George Barth Geller Distinguished Professor of Immunology, Immunology, Basic Science Departments 2020
- Professor of Immunology, Immunology, Basic Science Departments 2003
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 2012
Contact Information
- 318 Jones Bldg, Durham, NC 27710
- Duke Box 3010, Durham, NC 27710
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krang001@mc.duke.edu
(919) 684-4985
- Background
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Education, Training, & Certifications
- Ph.D., Harvard University 1982
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Previous Appointments & Affiliations
- Chair, Department of Immunology, Immunology, Basic Science Departments 2010 - 2022
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 1990 - 2021
- Mary Bernheim Distinguished Professor of Medicine, Immunology, Basic Science Departments 2010 - 2020
- Interim Chair, Department of Immunology, Immunology, Basic Science Departments 2009 - 2010
- Associate Professor of Immunology with Tenure, Immunology, Basic Science Departments 1995 - 2003
- Associate Professor of Immunology, Immunology, Basic Science Departments 1992 - 1995
- Associate Professor of Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 1990 - 1992
- Recognition
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Awards & Honors
- Expertise
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Subject Headings
- Academic Medical Centers
- Acetylation
- Alanine
- Alleles
- Amino Acid Sequence
- Amino Acids
- Animals
- Antibodies, Monoclonal
- Antibody Diversity
- Antibody Specificity
- Antigen-Antibody Reactions
- Antigens, CD3
- Antigens, CD4
- Antigens, CD8
- Antigens, Surface
- Arthritis, Rheumatoid
- B-Lymphocytes
- Base Sequence
- Binding Sites
- Binding, Competitive
- Biological Factors
- Biopolymers
- Blotting, Northern
- Blotting, Southern
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- CHO Cells
- COS Cells
- Calcium
- Carrier Proteins
- Cell Adhesion
- Cell Cycle Proteins
- Cell Differentiation
- Cell Division
- Cell Line
- Cell Line, Transformed
- Cell Lineage
- Cell Membrane
- Cell Movement
- Cell Nucleus
- Cell Survival
- Cells, Cultured
- Chemical Phenomena
- Chemical Precipitation
- Chemistry
- Chemokine CCL1
- Chemokine CCL2
- Chemokine CCL3
- Chemokine CCL4
- Chemokines
- Chemokines, CC
- Chemotactic Factors
- Chemotaxis, Leukocyte
- Child
- Chromatin
- Chromatin Assembly and Disassembly
- Chromatin Immunoprecipitation
- Chromosomal Proteins, Non-Histone
- Clone Cells
- Cloning, Molecular
- Cyanogen Bromide
- Cytokines
- Cytotoxicity, Immunologic
- DNA
- DNA Damage
- DNA Footprinting
- DNA Methylation
- DNA Nucleotidyltransferases
- DNA Repair
- DNA-Binding Proteins
- Deoxyribonuclease I
- Down-Regulation
- Drosophila
- Electrophoresis
- Endocytosis
- Enhancer Elements, Genetic
- Epitopes
- Exons
- Extracellular Space
- Feedback, Physiological
- Female
- Fetus
- Fibroblasts
- Fluorescent Antibody Technique
- Gangliosides
- Gene Expression
- Gene Expression Regulation
- Gene Frequency
- Gene Rearrangement
- Gene Rearrangement, B-Lymphocyte
- Gene Rearrangement, T-Lymphocyte
- Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
- Gene Rearrangement, delta-Chain T-Cell Antigen Receptor
- Gene Targeting
- Genes
- Genes, Immunoglobulin
- Genes, RAG-1
- Genes, Switch
- Genes, T-Cell Receptor
- Genes, T-Cell Receptor alpha
- Genes, T-Cell Receptor beta
- Genes, T-Cell Receptor delta
- Genetic Linkage
- Genetic Loci
- Genetic Variation
- Genotype
- Germ Cells
- Glycoproteins
- Glycosaminoglycans
- Glycosides
- Glycosylphosphatidylinositols
- HLA Antigens
- HMGB1 Protein
- Heparin
- Histone-Lysine N-Methyltransferase
- Histones
- Homeodomain Proteins
- Humans
- Hydrogen-Ion Concentration
- Hydroxylamines
- Image Processing, Computer-Assisted
- Immune Sera
- Immune System Phenomena
- Immunoglobulin Fragments
- Immunoglobulin G
- Immunoglobulin Joining Region
- Immunoglobulin Variable Region
- Immunologic Deficiency Syndromes
- In Situ Hybridization, Fluorescence
- Inflammation
- Interleukin-1
- Intracellular Signaling Peptides and Proteins
- Isoelectric Point
- Jurkat Cells
- Killer Cells, Natural
- Leukemia
- Lipopolysaccharides
- Liver Neoplasms, Experimental
- Lymphocyte Activation
- Lymphocytes
- Lymphoid Enhancer-Binding Factor 1
- Macromolecular Substances
- Macrophage Inflammatory Proteins
- Major Histocompatibility Complex
- Male
- Mast Cells
- Membrane Proteins
- Methyltransferases
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Mice, Mutant Strains
- Mice, Transgenic
- Microscopy, Confocal
- Models, Genetic
- Models, Molecular
- Molecular Sequence Data
- Molecular Weight
- Monocytes
- Multiprotein Complexes
- Mutagenesis
- Mutagenesis, Insertional
- Mutation
- N-Formylmethionine Leucyl-Phenylalanine
- Neoplasm Proteins
- Neutrophils
- Nuclear Proteins
- Nucleic Acid Conformation
- Nucleic Acid Hybridization
- Nucleosomes
- Nucleotide Mapping
- Oligosaccharides
- Organ Specificity
- Palmitic Acids
- Peptide Fragments
- Peptides
- Phenotype
- Phosphoproteins
- Phosphorylation
- Plasma
- Plasmids
- Point Mutation
- Polymorphism, Genetic
- Precipitin Tests
- Promoter Regions, Genetic
- Protein Binding
- Protein Methyltransferases
- Protein Precursors
- Protein Sorting Signals
- Quantitative Trait Loci
- RNA Splicing
- RNA, Messenger
- Receptors, Antigen, B-Cell
- Receptors, Antigen, T-Cell
- Receptors, Antigen, T-Cell, alpha-beta
- Receptors, Antigen, T-Cell, gamma-delta
- Receptors, Cytoplasmic and Nuclear
- Recombinant Fusion Proteins
- Recombinant Proteins
- Recombinases
- Recombination, Genetic
- Regulatory Sequences, Nucleic Acid
- Repressor Proteins
- Restriction Mapping
- Retroviridae
- Reverse Transcriptase Polymerase Chain Reaction
- Selection, Genetic
- Sequence Alignment
- Sequence Deletion
- Severe Combined Immunodeficiency
- Signal Transduction
- Solubility
- Species Specificity
- Specific Pathogen-Free Organisms
- Spleen
- Structure-Activity Relationship
- T-Lymphocyte Subsets
- T-Lymphocytes
- Thymocytes
- Thymus
- Thymus Gland
- Time Factors
- Transcription Factors
- Transcription, Genetic
- Transduction, Genetic
- Transfection
- Trypsinogen
- Tumor Cells, Cultured
- V(D)J Recombination
- VDJ Exons
- VDJ Recombinases
- Research
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Selected Grants
- Clinical and Genetic of Monomorphic Epitheliotropic Intestinal T Cell Lymphoma awarded by National Institutes of Health 2023 - 2027
- Basic Immunology Training Program awarded by National Institutes of Health 2020 - 2025
- Chromatin regulation of TCR locus V(D)J recombination awarded by National Institutes of Health 2020 - 2025
- Advanced Immunobiology Traning Program for Surgeons awarded by National Institutes of Health 2019 - 2024
- Control of TCR Delta and TCR Alpha Rearrangement awarded by National Institutes of Health 1989 - 2021
- Organization and Function of Cellular Structure awarded by National Institutes of Health 1975 - 2020
- Center for Molecular & Cellular Studies of Ped Disease awarded by National Institutes of Health 2003 - 2018
- Training Program in Inflammatory and Immunological Diseases awarded by National Institutes of Health 1980 - 2017
- Control of TCR V Beta Rearrangement & Allelic Exclusion awarded by National Institutes of Health 2001 - 2017
- The role of BATF in allergic inflammation and anti-helminth immunity awarded by National Institutes of Health 2015 - 2016
- Orphan Nuclear Receptor in Thymocyte Differentiation awarded by National Institutes of Health 2002 - 2007
- Structure And Function Of I-309 And Other Chemokines awarded by National Institutes of Health 1996 - 2002
- Control Of Tcr * And Trc * Gene Rearrangement awarded by National Institutes of Health 1994 - 1998
- Control Of Tcr Delta And Tcr Alpha Rearrangement awarded by National Institutes of Health 1989 - 1998
- Human Gamma Delta T Cell Receptor awarded by National Institutes of Health 1993 - 1994
- Human Ganna Delta T Cell Receptor awarded by National Institutes of Health 1990 - 1994
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External Relationships
- Emory University School of Medicine
- WW Norton
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Dauphars DJ, Wu G, Bassing CH, Krangel MS. Methods for Study of Mouse T Cell Receptor α and β Gene Rearrangements. Methods Mol Biol. 2023;2580:261–82.Full Text Link to Item
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Dauphars DJ, Mihai A, Wang L, Zhuang Y, Krangel MS. Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire. J Exp Med. 2022 Feb 7;219(2).Full Text Link to Item
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Karimi MM, Guo Y, Cui X, Pallikonda HA, Horková V, Wang Y-F, et al. The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat Commun. 2021 Jan 4;12(1):99.Full Text Link to Item
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Zhao H, Li Z, Zhu Y, Bian S, Zhang Y, Qin L, et al. A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus. Nucleic Acids Res. 2020 Sep 25;48(17):9621–36.Full Text Link to Item
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Krangel MS. RSSs set the odds for exclusion. J Exp Med. 2020 Sep 7;217(9).Full Text Link to Item
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Naik AK, Byrd AT, Lucander ACK, Krangel MS. Hierarchical assembly and disassembly of a transcriptionally active RAG locus in CD4+CD8+ thymocytes. J Exp Med. 2019 Jan 7;216(1):231–43.Full Text Link to Item
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Chen S, Krangel MS. Diversification of the TCR β Locus Vβ Repertoire by CTCF. Immunohorizons. 2018 Dec;2(11):377–83.Full Text Link to Item
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Chen S, Luperchio TR, Wong X, Doan EB, Byrd AT, Roy Choudhury K, et al. A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus. Cell Rep. 2018 Nov 13;25(7):1729-1740.e6.Full Text Link to Item
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Loguercio S, Barajas-Mora EM, Shih H-Y, Krangel MS, Feeney AJ. Variable Extent of Lineage-Specificity and Developmental Stage-Specificity of Cohesin and CCCTC-Binding Factor Binding Within the Immunoglobulin and T Cell Receptor Loci. Front Immunol. 2018;9:425.Full Text Link to Item
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McMurry MT, Krangel MS. Pillars Article: A Role for Histone Acetylation in the Developmental Regulation of V(D)J Recombination. Science. 2000. 287: 495-498. J Immunol. 2017 Jul 1;199(1):5–8.Link to Item
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Carico ZM, Roy Choudhury K, Zhang B, Zhuang Y, Krangel MS. Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire. Cell Rep. 2017 Jun 6;19(10):2157–73.Full Text Link to Item
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Chen L, Zhao L, Alt FW, Krangel MS. An Ectopic CTCF Binding Element Inhibits Tcrd Rearrangement by Limiting Contact between Vδ and Dδ Gene Segments. J Immunol. 2016 Oct 15;197(8):3188–97.Full Text Link to Item
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Zhao L, Frock RL, Du Z, Hu J, Chen L, Krangel MS, et al. Orientation-specific RAG activity in chromosomal loop domains contributes to Tcrd V(D)J recombination during T cell development. J Exp Med. 2016 Aug 22;213(9):1921–36.Full Text Link to Item
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Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, et al. Pillars Article: Identification of a Putative Second T-cell Receptor. Nature. 1986. 322: 145-149. J Immunol. 2016 May 1;196(9):3509–13.Link to Item
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Krangel MS. The Ties that Bind (the Igh Locus). Trends Genet. 2016 May;32(5):253–5.Full Text Link to Item
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Chen L, Foreman DP, Sant’Angelo DB, Krangel MS. Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53. J Immunol. 2016 Mar 15;196(6):2572–82.Full Text Link to Item
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Thornton TM, Delgado P, Chen L, Salas B, Krementsov D, Fernandez M, et al. Inactivation of nuclear GSK3β by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response. Nat Commun. 2016 Jan 29;7:10553.Full Text Link to Item
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Krangel MS. Beyond Hypothesis: Direct Evidence That V(D)J Recombination Is Regulated by the Accessibility of Chromatin Substrates. J Immunol. 2015 Dec 1;195(11):5103–5.Full Text Link to Item
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Chen L, Carico Z, Shih H-Y, Krangel MS. A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRδ and TCRα repertoires. Nat Immunol. 2015 Oct;16(10):1085–93.Full Text Open Access Copy Link to Item
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Hao B, Naik AK, Watanabe A, Tanaka H, Chen L, Richards HW, et al. An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development. J Exp Med. 2015 May 4;212(5):809–24.Full Text Link to Item
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del Blanco B, Angulo Ú, Krangel MS, Hernández-Munain C. T-cell receptor α enhancer is inactivated in αβ T lymphocytes. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1744–53.Full Text Link to Item
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Boudil A, Matei IR, Shih HY, Bogdanoski G, Yuan JS, Chang SG, et al. IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection. Nature Immunology. 2015 Mar 19;16(4):397–405.Full Text
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Naik AK, Hawwari A, Krangel MS. Specification of Vδ and Vα usage by Tcra/Tcrd locus V gene segment promoters. J Immunol. 2015 Jan 15;194(2):790–4.Full Text Link to Item
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Majumder K, Koues OI, Chan EAW, Kyle KE, Horowitz JE, Yang-Iott K, et al. Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element. J Exp Med. 2015 Jan 12;212(1):107–20.Full Text Link to Item
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Carico Z, Krangel MS. Chromatin Dynamics and the Development of the TCRα and TCRδ Repertoires. Adv Immunol. 2015;128:307–61.Full Text Link to Item
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Tubbs AT, Dorsett Y, Chan E, Helmink B, Lee B-S, Hung P, et al. KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G₁-phase lymphocytes. Mol Cell Biol. 2014 Aug;34(15):2811–21.Full Text Link to Item
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Chan EAW, Teng G, Corbett E, Choudhury KR, Bassing CH, Schatz DG, et al. Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):E4628–37.Full Text Link to Item
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Shih H-Y, Krangel MS. Chromatin architecture, CCCTC-binding factor, and V(D)J recombination: managing long-distance relationships at antigen receptor loci. J Immunol. 2013 May 15;190(10):4915–21.Full Text Link to Item
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Callen E, Faryabi RB, Luckey M, Hao B, Daniel JA, Yang W, et al. The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration. Immunity. 2012 Dec 14;37(6):971–85.Full Text Link to Item
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Shih H-Y, Verma-Gaur J, Torkamani A, Feeney AJ, Galjart N, Krangel MS. Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):E3493–502.Full Text Link to Item
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Seitan VC, Krangel MS, Merkenschlager M. Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement. Trends Immunol. 2012 Apr;33(4):153–9.Full Text Link to Item
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Kondilis-Mangum HD, Shih H-Y, Mahowald G, Sleckman BP, Krangel MS. Regulation of TCRβ allelic exclusion by gene segment proximity and accessibility. J Immunol. 2011 Dec 15;187(12):6374–81.Full Text Link to Item
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Hao B, Krangel MS. Long-distance regulation of fetal V(δ) gene segment TRDV4 by the Tcrd enhancer. J Immunol. 2011 Sep 1;187(5):2484–91.Full Text Link to Item
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Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, et al. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature. 2011 Aug 10;476(7361):467–71.Full Text Link to Item
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Krangel MS. Immunology at Duke: 2011. Immunol Res. 2011 Apr;49(1–3):1–2.Full Text Link to Item
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Shih H-Y, Hao B, Krangel MS. Orchestrating T-cell receptor α gene assembly through changes in chromatin structure and organization. Immunol Res. 2011 Apr;49(1–3):192–201.Full Text Link to Item
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Carabana J, Watanabe A, Hao B, Krangel MS. A barrier-type insulator forms a boundary between active and inactive chromatin at the murine TCRβ locus. J Immunol. 2011 Mar 15;186(6):3556–62.Full Text Link to Item
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Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, et al. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. J Exp Med. 2010 Dec 20;207(13):2809–16.Full Text Link to Item
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Shih H-Y, Krangel MS. Distinct contracted conformations of the Tcra/Tcrd locus during Tcra and Tcrd recombination. J Exp Med. 2010 Aug 30;207(9):1835–41.Full Text Link to Item
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Kondilis-Mangum HD, Cobb RM, Osipovich O, Srivatsan S, Oltz EM, Krangel MS. Transcription-dependent mobilization of nucleosomes at accessible TCR gene segments in vivo. J Immunol. 2010 Jun 15;184(12):6970–7.Full Text Link to Item
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Vazquez BN, Laguna T, Carabana J, Krangel MS, Lauzurica P. CD69 gene is differentially regulated in T and B cells by evolutionarily conserved promoter-distal elements. J Immunol. 2009 Nov 15;183(10):6513–21.Full Text Link to Item
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Krangel MS. Mechanics of T cell receptor gene rearrangement. Curr Opin Immunol. 2009 Apr;21(2):133–9.Full Text Link to Item
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Abarrategui I, Krangel MS. Germline transcription: a key regulator of accessibility and recombination. Adv Exp Med Biol. 2009;650:93–102.Full Text Link to Item
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Schlimgen RJ, Reddy KL, Singh H, Krangel MS. Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments. Nat Immunol. 2008 Jul;9(7):802–9.Full Text Link to Item
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Abarrategui I, Krangel MS. Noncoding transcription controls downstream promoters to regulate T-cell receptor alpha recombination. Embo J. 2007 Oct 17;26(20):4380–90.Full Text Link to Item
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Hager E, Hawwari A, Matsuda JL, Krangel MS, Gapin L. Multiple constraints at the level of TCRalpha rearrangement impact Valpha14i NKT cell development. J Immunol. 2007 Aug 15;179(4):2228–34.Full Text Link to Item
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Krangel MS. T cell development: better living through chromatin. Nat Immunol. 2007 Jul;8(7):687–94.Full Text Link to Item
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Roberts JL, Lauritsen JPH, Cooney M, Parrott RE, Sajaroff EO, Win CM, et al. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. Blood. 2007 Apr 15;109(8):3198–206.Full Text Link to Item
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Hawwari A, Krangel MS. Role for rearranged variable gene segments in directing secondary T cell receptor alpha recombination. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):903–7.Full Text Link to Item
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Abarrategui I, Krangel MS. Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol. 2006 Oct;7(10):1109–15.Full Text Link to Item
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Jackson AM, Krangel MS. A role for MAPK in feedback inhibition of Tcrb recombination. J Immunol. 2006 Jun 1;176(11):6824–30.Full Text Link to Item
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Krangel MS, Carabana J, Abarrategui I. Some nuts are tougher to crack than others. Immunity. 2006 Apr;24(4):361–3.Full Text Link to Item
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Jackson AM, Krangel MS. Turning T-cell receptor beta recombination on and off: more questions than answers. Immunol Rev. 2006 Feb;209:129–41.Full Text Link to Item
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Jackson AM, Krangel MS. Allele-specific regulation of TCR beta variable gene segment chromatin structure. J Immunol. 2005 Oct 15;175(8):5186–91.Full Text Link to Item
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Hawwari A, Krangel MS. Regulation of TCR delta and alpha repertoires by local and long-distance control of variable gene segment chromatin structure. J Exp Med. 2005 Aug 15;202(4):467–72.Full Text Link to Item
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Hawwari A, Bock C, Krangel MS. Regulation of T cell receptor alpha gene assembly by a complex hierarchy of germline Jalpha promoters. Nat Immunol. 2005 May;6(5):481–9.Full Text Link to Item
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Carabana J, Ortigoza E, Krangel MS. Regulation of the murine Ddelta2 promoter by upstream stimulatory factor 1, Runx1, and c-Myb. J Immunol. 2005 Apr 1;174(7):4144–52.Full Text Link to Item
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Jackson A, Kondilis HD, Khor B, Sleckman BP, Krangel MS. Regulation of T cell receptor beta allelic exclusion at a level beyond accessibility. Nat Immunol. 2005 Feb;6(2):189–97.Full Text Link to Item
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Balmelle N, Zamarreño N, Krangel MS, Hernández-Munain C. Developmental activation of the TCR alpha enhancer requires functional collaboration among proteins bound inside and outside the core enhancer. J Immunol. 2004 Oct 15;173(8):5054–63.Full Text Link to Item
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Krangel MS, Carabana J, Abbarategui I, Schlimgen R, Hawwari A. 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. Immunol Rev. 2004 Aug;200:224–32.Full Text Link to Item
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Osipovich O, Milley R, Meade A, Tachibana M, Shinkai Y, Krangel MS, et al. Targeted inhibition of V(D)J recombination by a histone methyltransferase. Nat Immunol. 2004 Mar;5(3):309–16.Full Text Link to Item
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Krangel MS. Gene segment selection in V(D)J recombination: accessibility and beyond. Nat Immunol. 2003 Jul;4(7):624–30.Full Text Link to Item
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Hernández-Munain C, Krangel MS. 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. J Immunol. 2002 Oct 15;169(8):4362–9.Full Text Link to Item
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Sikes ML, Meade A, Tripathi R, Krangel MS, Oltz EM. Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12309–14.Full Text Link to Item
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Guo J, Hawwari A, Li H, Sun Z, Mahanta SK, Littman DR, et al. Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes. Nat Immunol. 2002 May;3(5):469–76.Full Text Link to Item
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Tripathi R, Jackson A, Krangel MS. A change in the structure of Vbeta chromatin associated with TCR beta allelic exclusion. J Immunol. 2002 Mar 1;168(5):2316–24.Full Text Link to Item
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Sleckman BP, Carabana J, Zhong X, Krangel MS. Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus. Immunology. 2001 Sep;104(1):11–8.Full Text Link to Item
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Krangel MS. V(D)J recombination becomes accessible. J Exp Med. 2001 Apr 2;193(7):F27–30.Full Text Link to Item
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Patel DD, Koopmann W, Imai T, Whichard LP, Yoshie O, Krangel MS. Chemokines have diverse abilities to form solid phase gradients. Clin Immunol. 2001 Apr;99(1):43–52.Full Text Link to Item
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Ali H, Ahamed J, Hernandez-Munain C, Baron JL, Krangel MS, Patel DD. Chemokine production by G protein-coupled receptor activation in a human mast cell line: roles of extracellular signal-regulated kinase and NFAT. J Immunol. 2000 Dec 15;165(12):7215–23.Full Text Link to Item
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Bukowski JF, Roncarolo MG, Spits H, Krangel MS, Morita CT, Brenner MB, et al. T cell receptor-dependent activation of human lymphocytes through cell surface ganglioside GT1b: implications for innate immunity. Eur J Immunol. 2000 Nov;30(11):3199–206.Full Text Link to Item
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McMurry MT, Krangel MS. A role for histone acetylation in the developmental regulation of VDJ recombination. Science. 2000 Jan 21;287(5452):495–8.Full Text Link to Item
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Krangel MS, McMurry MT, Hernandez-Munain C, Zhong XP, Carabana J. Accessibility control of T cell receptor gene rearrangement in developing thymocytes. The TCR alpha/delta locus. Immunol Res. 2000;22(2–3):127–35.Full Text Link to Item
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Zhong XP, Carabaña J, Krangel MS. Flanking nuclear matrix attachment regions synergize with the T cell receptor delta enhancer to promote V(D)J recombination. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11970–5.Full Text Link to Item
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Koopmann W, Ediriwickrema C, Krangel MS. Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta. J Immunol. 1999 Aug 15;163(4):2120–7.Link to Item
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Zhong XP, Krangel MS. Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes. J Immunol. 1999 Jul 1;163(1):295–300.Link to Item
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Hernández-Munain C, Sleckman BP, Krangel MS. A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation. Immunity. 1999 Jun;10(6):723–33.Full Text Link to Item
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Hernandez-Munain C, McMurry MT, Krangel MS. Regulation of chromatin accessibility for V(D)J recombination. Cold Spring Harb Symp Quant Biol. 1999;64:183–9.Full Text Link to Item
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Krangel MS, Hernandez-Munain C, Lauzurica P, McMurry M, Roberts JL, Zhong XP. Developmental regulation of V(D)J recombination at the TCR alpha/delta locus. Immunol Rev. 1998 Oct;165:131–47.Full Text Link to Item
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Hernandez-Munain C, Roberts JL, Krangel MS. Cooperation among multiple transcription factors is required for access to minimal T-cell receptor alpha-enhancer chromatin in vivo. Mol Cell Biol. 1998 Jun;18(6):3223–33.Full Text Link to Item
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McMurry MT, Hernandez-Munain C, Lauzurica P, Krangel MS. Enhancer control of local accessibility to V(D)J recombinase. Mol Cell Biol. 1997 Aug;17(8):4553–61.Full Text Link to Item
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Zhong XP, Krangel MS. An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5219–24.Full Text Link to Item
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Koopmann W, Krangel MS. Identification of a glycosaminoglycan-binding site in chemokine macrophage inflammatory protein-1alpha. J Biol Chem. 1997 Apr 11;272(15):10103–9.Full Text Link to Item
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Lauzurica P, Zhong XP, Krangel MS, Roberts JL. Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2. J Exp Med. 1997 Apr 7;185(7):1193–201.Full Text Link to Item
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Selvan RS, Zhou LJ, Krangel MS. Regulation of I-309 gene expression in human monocytes by endogenous interleukin-1. Eur J Immunol. 1997 Mar;27(3):687–94.Full Text Link to Item
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Roberts JL, Lauzurica P, Krangel MS. Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer. J Exp Med. 1997 Jan 6;185(1):131–40.Full Text Link to Item
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Hernández-Munain C, Lauzurica P, Krangel MS. Regulation of T cell receptor delta gene rearrangement by c-Myb. J Exp Med. 1996 Jan 1;183(1):289–93.Full Text Link to Item
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Redondo JM, Hernandez-Munain C, Krangel MS. Transcriptional regulation of the human T cell receptor delta gene. Immunobiology. 1995 Jul;193(2–4):288–92.Full Text Link to Item
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Hernandez-Munain C, Krangel MS. c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor delta enhancer. Mol Cell Biol. 1995 Jun;15(6):3090–9.Full Text Link to Item
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Hernandez-Munain C, Krangel MS. Erratum: c-Myb and core-binding factor/PEBP2 display functional synergy but bind independently to adjacent sites in the T-cell receptor δ enhancer (Molecular and Cellular Biology (1995) 15:6 (3095)). Molecular and Cellular Biology. 1995 Jan 1;15(8):4659.
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Paolini JF, Willard D, Consler T, Luther M, Krangel MS. The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations. J Immunol. 1994 Sep 15;153(6):2704–17.Link to Item
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Buchwalder A, Krangel MS, Hao P, Diamond DJ. Immunochemical and molecular analysis of antigen binding to lipid anchored and soluble forms of an MHC independent human alpha/beta T cell receptor. Mol Immunol. 1994 Aug;31(11):857–72.Full Text Link to Item
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Lauzurica P, Krangel MS. Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers. J Exp Med. 1994 Jun 1;179(6):1913–21.Full Text Link to Item
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Selvan RS, Butterfield JH, Krangel MS. Expression of multiple chemokine genes by a human mast cell leukemia. J Biol Chem. 1994 May 13;269(19):13893–8.Link to Item
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Lauzurica P, Krangel MS. Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor delta transgene. J Exp Med. 1994 Jan 1;179(1):43–55.Full Text Link to Item
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Hernandez-Munain C, Krangel MS. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Mol Cell Biol. 1994 Jan;14(1):473–83.Full Text Link to Item
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Redondo JM, Pfohl JL, Hernandez-Munain C, Wang S, Speck NA, Krangel MS. Indistinguishable nuclear factor binding to functional core sites of the T-cell receptor delta and murine leukemia virus enhancers. Mol Cell Biol. 1992 Nov;12(11):4817–23.Full Text Link to Item
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Miller MD, Krangel MS. The human cytokine I-309 is a monocyte chemoattractant. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2950–4.Full Text Link to Item
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Miller MD, Krangel MS. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1–2):17–46.Link to Item
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Redondo JM, Pfohl JL, Krangel MS. Identification of an essential site for transcriptional activation within the human T-cell receptor delta enhancer. Mol Cell Biol. 1991 Nov;11(11):5671–80.Full Text Link to Item
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Spits H, Yssel H, Brockelhurst C, Krangel M. Evidence for controlled gene rearrangements and cytokine production during development of human TCR gamma delta+ lymphocytes. Curr Top Microbiol Immunol. 1991;173:47–55.Full Text Link to Item
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Miller MD, Wilson SD, Dorf ME, Seuanez HN, O’Brien SJ, Krangel MS. Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines. J Immunol. 1990 Oct 15;145(8):2737–44.Link to Item
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Krangel MS, Yssel H, Brocklehurst C, Spits H. A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production. J Exp Med. 1990 Sep 1;172(3):847–59.Full Text Link to Item
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Redondo JM, Hata S, Brocklehurst C, Krangel MS. A T cell-specific transcriptional enhancer within the human T cell receptor delta locus. Science. 1990 Mar 9;247(4947):1225–9.Full Text Link to Item
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Solomon KR, Krangel MS, McLean J, Brenner MB, Band H. Human T cell receptor-gamma and -delta chain pairing analyzed by transfection of a T cell receptor-delta negative mutant cell line. J Immunol. 1990 Feb 1;144(3):1120–6.Link to Item
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Miller MD, Hata S, De Waal Malefyt R, Krangel MS. A novel polypeptide secreted by activated human T lymphocytes. J Immunol. 1989 Nov 1;143(9):2907–16.Link to Item
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Band H, Hochstenbach F, Parker CM, McLean J, Krangel MS, Brenner MB. Expression of human T cell receptor-gamma delta structural forms. J Immunol. 1989 May 15;142(10):3627–33.Link to Item
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Brenner MB, Hochstenbach F, Band H, Parker C, McLean J, Hata S, et al. Human T cell receptor gamma delta structure. Adv Exp Med Biol. 1989;254:17–9.Link to Item
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Hata S, Clabby M, Devlin P, Spits H, De Vries JE, Krangel MS. Diversity and organization of human T cell receptor delta variable gene segments. J Exp Med. 1989 Jan 1;169(1):41–57.Full Text Link to Item
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Satyanarayana K, Hata S, Devlin P, Roncarolo MG, De Vries JE, Spits H, et al. Genomic organization of the human T-cell antigen-receptor alpha/delta locus. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8166–70.Full Text Link to Item
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Hata S, Satyanarayana K, Devlin P, Band H, McLean J, Strominger JL, et al. Extensive junctional diversity of rearranged human T cell receptor delta genes. Science. 1988 Jun 10;240(4858):1541–4.Full Text Link to Item
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Brenner MB, Strominger JL, Krangel MS. The γδT Cell Receptor. Advances in Immunology. 1988 Jan 1;43(C):133–92.Full Text
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Brenner MB, Strominger JL, Krangel MS. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–92.Link to Item
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Band H, Hochstenbach F, McLean J, Hata S, Krangel MS, Brenner MB. Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit. Science. 1987 Oct 30;238(4827):682–4.Full Text Link to Item
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Hata S, Brenner MB, Krangel MS. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–82.Full Text Link to Item
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Modlin RL, Brenner MB, Krangel MS, Duby AD, Bloom BR. T-cell receptors of human suppressor cells. Nature. 1987 Oct 8;329(6139):541–5.Full Text Link to Item
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Krangel MS. Two forms of HLA class I molecules in human plasma. Hum Immunol. 1987 Oct;20(2):155–65.Full Text Link to Item
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Krangel MS, Band H, Hata S, McLean J, Brenner MB. Structurally divergent human T cell receptor gamma proteins encoded by distinct C gamma genes. Science. 1987 Jul 3;237(4810):64–7.Full Text Link to Item
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Krangel MS, Bierer BE, Devlin P, Clabby M, Strominger JL, McLean J, et al. T3 glycoprotein is functional although structurally distinct on human T-cell receptor gamma T lymphocytes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3817–21.Full Text Link to Item
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Krangel MS. Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. J Exp Med. 1987 Apr 1;165(4):1141–59.Full Text Link to Item
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Brenner MB, McLean J, Scheft H, Riberdy J, Ang SL, Seidman JG, et al. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–94.Full Text Link to Item
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Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, et al. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–9.Full Text Link to Item
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Krangel MS. Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway. J Exp Med. 1986 May 1;163(5):1173–90.Full Text Link to Item
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Lopez de Castro JA, Barbosa JA, Krangel MS, Biro PA, Strominger JL. Structural analysis of the functional sites of class I HLA antigens. Immunol Rev. 1985 Jul;85:149–68.Full Text Link to Item
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Krangel MS. Unusual RNA splicing generates a secreted form of HLA-A2 in a mutagenized B lymphoblastoid cell line. Embo J. 1985 May;4(5):1205–10.Full Text Link to Item
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Taketani S, Krangel MS, Spits H, de Vries J, Strominger JL. Structural analysis of an HLA-B7 antigen variant detected by cytotoxic T lymphocytes. J Immunol. 1984 Aug;133(2):816–21.Link to Item
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Kaufman JF, Krangel MS, Strominger JL. Cysteines in the transmembrane region of major histocompatibility complex antigens are fatty acylated via thioester bonds. J Biol Chem. 1984 Jun 10;259(11):7230–8.Link to Item
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Krangel MS, Pious D, Strominger JL. Characterization of a B lymphoblastoid cell line mutant that secretes HLA-A2. J Immunol. 1984 Jun;132(6):2984–91.Link to Item
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Taketani S, Krangel MS, Pious D, Strominger JL. Structural analysis of HLA-A2 antigen from immunoselected mutant 8.6.1: further definition of an HLA-A2-specific serological determinant. J Immunol. 1983 Dec;131(6):2935–8.Link to Item
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Ware CF, Krangel MS, Pious D, Burakoff SJ, Strominger JL. Recognition of HLA-A2 mutant and variant target cells by an HLA-A2 allospecific human cytotoxic T lymphocyte line. J Immunol. 1983 Sep;131(3):1312–7.Link to Item
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Krangel MS, Biddison WE, Strominger JL. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes. II. Variant DK1: evidence for a discrete CTL recognition region. J Immunol. 1983 Apr;130(4):1856–62.Link to Item
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Krangel MS, Taketani S, Pious D, Strominger JL. HLA-A2 mutants immunoselected in vitro. Definition of residues contributing to an HLA-A2-specific serological determinant. J Exp Med. 1983 Jan 1;157(1):324–36.Full Text Link to Item
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Pious D, Krangel MS, Dixon LL, Parham P, Strominger JL. HLA antigen structural gene mutants selected with an allospecific monoclonal antibody. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7832–6.Full Text Link to Item
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Krangel MS, Taketani S, Biddison WE, Strong DM, Strominger JL. Comparative structural analysis of HLA-A2 antigens distinguishable by cytotoxic T lymphocytes: variants M7 and DR1. Biochemistry. 1982 Nov 23;21(24):6313–21.Full Text Link to Item
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Biddison WE, Kostyu DD, Strominger JL, Krangel MS. Delineation of immunologically and biochemically distinct HLA-A2 antigens. J Immunol. 1982 Aug;129(2):730–4.Link to Item
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Krangel MS, Pious D, Strominger JL. Human histocompatibility antigen mutants immunoselected in vitro. Biochemical analysis of a mutant which synthesizes an altered HLA-A2 heavy chain. J Biol Chem. 1982 May 10;257(9):5296–305.Link to Item
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Biddison WE, Krangel MS, Strominger JL, Ward FE, Shearer GM, Shaw S. Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules. Hum Immunol. 1980 Oct;1(3):225–32.Full Text Link to Item
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Krangel MS, Orr HT, Strominger JL. Structure, function, and biosynthesis of the major human histocompatibility antigens (HLA-A and HLA-B). Scand J Immunol. 1980;11(6):561–71.Full Text Link to Item
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Krangel MS, Orr HT, Strominger JL. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell. 1979 Dec;18(4):979–91.Full Text Link to Item
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Book Sections
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Krangel MS, Schlissel MS. Allelic Exclusion, Isotypic Exclusion, and the Developmental Regulation of V(D)J Recombination. In: Molecular Biology of B Cells. 2004. p. 127–40.Full Text
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