title: Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.forename: Gamze
authors.initials: G
authors.lastname: Isitman
authors.forename: Marjon
authors.initials: M
authors.lastname: Navis
authors.forename: Marit
authors.initials: M
authors.lastname: Kramski
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Center
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015686:Gene Products, env / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D000939:Epitopes; D015686:Gene Products, env