Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 208, Issue 11, Pages 2237-2249Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110363
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Funding
- Center for HIV/AIDS Vaccine Immunology National Institute of Allergy and Infectious Disease (NIAID) [U19 AI067854]
- NIAID [P01 AI061734, U54 AI065359]
- Bill and Melinda Gates Foundation
- National Institutes of Health [S10RR019145, UC6 AI058607, AI64518, P30 AI051445, AI051]
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The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is non-neutralizing 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.
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