Contribution of VH replacement products to the generation of anti-HIV antibodies

Hongyan Liao, Jun tao Guo, Miles D. Lange, Run Fan, Michael Zemlin, Kaihong Su, Yongjun Guan, Zhixin Zhang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

VH replacement occurs through RAG-mediated secondary recombination to change unwanted IgH genes and diversify antibody repertoire. The biological significance of VH replacement remains to be explored. Here, we show that VH replacement products are highly enriched in IgH genes encoding anti-HIV antibodies, including anti-gp41, anti-V3 loop, anti-gp120, CD4i, and PGT antibodies. In particular, 73% of the CD4i antibodies and 100% of the PGT antibodies are encoded by potential VH replacement products. Such frequencies are significantly higher than those in IgH genes derived from HIV infected individuals or autoimmune patients. The identified VH replacement products encoding anti-HIV antibodies are highly mutated; the VH replacement "footprints" within CD4i antibodies preferentially encode negatively charged amino acids within the IgH CDR3; many IgH encoding PGT antibodies are likely generated from multiple rounds of VH replacement. Taken together, these findings uncovered a potentially significant contribution of VH replacement products to the generation of anti-HIV antibodies.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalClinical Immunology
Volume146
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Anti-HIV antibody
  • CD4i antibody
  • Gp120
  • IgH gene
  • V replacement

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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