Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure
Amy W. Chunga,1, Gamze Isitmana,1, Marjon Navisa, Marit Kramskia, Rob J. Centera, Stephen J. Kenta,b,c,1,2, and Ivan Stratova,b,c,1
+ Author Affiliations
aDepartment of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia;
bMelbourne Sexual Health Clinic, Carlton, VIC 3053, Australia; and
cInfectious Diseases Unit, Alfred Hospital, Prahran, VIC 3181, Australia
Edited by Peter C. Doherty, University of Melbourne, Parkville, VIC, Australia, and approved March 23, 2011 (received for review October 26, 2010)
【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.