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Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.

Publication ,  Journal Article
Kepler, TB; Liao, H-X; Alam, SM; Bhaskarabhatla, R; Zhang, R; Yandava, C; Stewart, S; Anasti, K; Kelsoe, G; Parks, R; Lloyd, KE; Stolarchuk, C ...
Published in: Cell Host Microbe
September 10, 2014

Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deletions (indels). Here we examined the propensity and functional requirement for indels within HIV-1 bnAbs. High-throughput sequencing of the immunoglobulin (Ig) VHDJH genes in HIV-1 infected and uninfected individuals revealed that the indel frequency was elevated among HIV-1-infected subjects, with no unique properties attributable to bnAb-producing individuals. This increased indel occurrence depended only on the frequency of SHM point mutations. Indel-encoded regions were generally proximal to antigen binding sites. Additionally, reconstruction of a HIV-1 CD4-binding site bnAb clonal lineage revealed that a large compound VHDJH indel was required for bnAb activity. Thus, vaccine development should focus on designing regimens targeted at sustained activation of bnAb lineages to achieve the required SHM and indel events.

Duke Scholars

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

September 10, 2014

Volume

16

Issue

3

Start / End Page

304 / 313

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Models, Molecular
  • Immunology
  • Immunoglobulins
  • INDEL Mutation
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • CD4-Positive T-Lymphocytes
 

Citation

APA
Chicago
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Kepler, T. B., Liao, H.-X., Alam, S. M., Bhaskarabhatla, R., Zhang, R., Yandava, C., … Haynes, B. F. (2014). Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host Microbe, 16(3), 304–313. https://doi.org/10.1016/j.chom.2014.08.006
Kepler, Thomas B., Hua-Xin Liao, S Munir Alam, Rekha Bhaskarabhatla, Ruijun Zhang, Chandri Yandava, Shelley Stewart, et al. “Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.Cell Host Microbe 16, no. 3 (September 10, 2014): 304–13. https://doi.org/10.1016/j.chom.2014.08.006.
Kepler TB, Liao H-X, Alam SM, Bhaskarabhatla R, Zhang R, Yandava C, et al. Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host Microbe. 2014 Sep 10;16(3):304–13.
Kepler, Thomas B., et al. “Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies.Cell Host Microbe, vol. 16, no. 3, Sept. 2014, pp. 304–13. Pubmed, doi:10.1016/j.chom.2014.08.006.
Kepler TB, Liao H-X, Alam SM, Bhaskarabhatla R, Zhang R, Yandava C, Stewart S, Anasti K, Kelsoe G, Parks R, Lloyd KE, Stolarchuk C, Pritchett J, Solomon E, Friberg E, Morris L, Karim SSA, Cohen MS, Walter E, Moody MA, Wu X, Altae-Tran HR, Georgiev IS, Kwong PD, Boyd SD, Fire AZ, Mascola JR, Haynes BF. Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host Microbe. 2014 Sep 10;16(3):304–313.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

September 10, 2014

Volume

16

Issue

3

Start / End Page

304 / 313

Location

United States

Related Subject Headings

  • Molecular Sequence Data
  • Models, Molecular
  • Immunology
  • Immunoglobulins
  • INDEL Mutation
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • CD4-Positive T-Lymphocytes