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J Exp Med. 2011 Oct 24;208(11):2237-49. doi: 10.1084/jem.20110363. Epub 2011 Oct 10.

Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

Author information

1
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. hliao@duke.edu

Abstract

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.

PMID:
21987658
PMCID:
PMC3201211
DOI:
10.1084/jem.20110363
[Indexed for MEDLINE]
Free PMC Article

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