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

AW Chung, G Isitman, M Navis… - Proceedings of the …, 2011 - National Acad Sciences
AW Chung, G Isitman, M Navis, M Kramski, RJ Center, SJ Kent, I Stratov
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences