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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: Implications for vaccine design
Journal of Virology, Volume 79, No. 8, Year 2005
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Description
Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HFV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent I60L variant all developed these responses. The I60L variant epitope was a stronger binder to HLA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Altfeld, Marcus A.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Allen, Todd M.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Frahm, Nicole
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Addo, Marylyn Martina
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Mothé, Bianca R.
United States, San Marcos
California State University San Marcos
Rathod, Almas
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Harlow, Jason Davis
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Yu, Xu G.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Sidney, John
United States, La Jolla
La Jolla Institute for Immunology
Alter, Galit
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Lichterfeld, Mathias D.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Sette, Alessandro D.
United States, La Jolla
La Jolla Institute for Immunology
Rosenberg, Eric S.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Goulder, Philip Jeremy Renshaw
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
United Kingdom, Oxford
Nuffield Department of Medicine
Brander, Christian
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 34
Authors: 16
Affiliations: 6
Identifiers
Doi:
10.1128/JVI.79.8.5000-5005.2005
ISSN:
0022538X
Research Areas
Genetics And Genomics
Infectious Diseases