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

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-inf...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 108; no. 18; pp. 7505 - 7510
Main Authors Chung, Amy W, Isitman, Gamze, Navis, Marjon, Kramski, Marit, Center, Rob J, Kent, Stephen J, Stratov, Ivan
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 03.05.2011
National Acad Sciences
Subjects
Amino acids
Antibodies
Antibody dependent cell cytotoxicity
Antibody-Dependent Cell Cytotoxicity - genetics
Antibody-Dependent Cell Cytotoxicity - immunology
Antibody-dependent cell-mediated cytotoxicity
Base Sequence
Biological Sciences
Cell activation
Cells
Cytotoxicity
Epitope Mapping
Epitopes
Epitopes - genetics
Epitopes - immunology
Flow Cytometry
Gene Products, env - genetics
Genetic mutation
HIV
HIV 1
HIV infections
HIV Infections - immunology
HIV-1 - immunology
Human immunodeficiency virus
Humans
Immune system
Immunity
Killer Cells, Natural - immunology
Lymphocyte Activation - immunology
Molecular Sequence Data
Natural killer cells
Neutralization Tests
Peptides
Plasmids - genetics
Pressure
Sequence Analysis, DNA
T lymphocytes
Toxicity
Vaccines
Viruses
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Summary: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.
Bibliography:http://dx.doi.org/10.1073/pnas.1016048108
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1A.W.C., G.I., S.J.K., and I.S. contributed equally to this work.
Edited by Peter C. Doherty, University of Melbourne, Parkville, VIC, Australia, and approved March 23, 2011 (received for review October 26, 2010)
Author contributions: A.W.C., M.N., R.J.C., S.J.K., and I.S. designed research; A.W.C., G.I., M.N., M.K., R.J.C., and I.S. performed research; and A.W.C. and S.J.K. wrote the paper.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1016048108