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Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure.

Chung AW, Isitman G, Navis M, Kramski M, Center RJ, Kent SJ, Stratov I

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  • Journal Proceedings of the National Academy of Sciences of the United States of America

  • Published 18 Apr 2011

  • Volume 108

  • ISSUE 18

  • Pagination 7505-10

  • DOI 10.1073/pnas.1016048108

Abstract

Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV is controversial. We hypothesized that significant pressure from HIV-specific ADCC would result in immune-escape variants. A series of ADCC epitopes in HIV-infected subjects to specific consensus strain HIV peptides were mapped using a flow cytometric assay for natural killer cell activation. We then compared the ADCC responses to the same peptide epitope derived from the concurrent HIV sequence(s) expressed in circulating virus. In 9 of 13 epitopes studied, ADCC antibodies were unable to recognize the concurrent HIV sequence. Our studies suggest ADCC responses apply significant immune pressure on the virus. This result has implications for the induction of ADCC responses by HIV vaccines.