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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure
AIDS Research and Human Retroviruses, Volume 24, No. 1, Year 2008
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Description
In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two alleles differ by only three amino acids in regions involved in HLA-peptide recognition. This study evaluated a cohort of over 1000 persons with chronic HIV clade C virus infection to determine whether clinical outcome differences associated with B*5801 (n = 93) and B*5802 ( n = 259) expression are associated with differences in HIV-1-specific CD8 + T cell responses. The overall breadth and magnitude of HIV-1-specific CD8+ T cell responses were lower in persons expressing B*5802, and epitope presentation by B*5802 contributed significantly less to the overall response as compared to B*5801- restricted CD8 + T cells. Moreover, viral load in B*5802-positive persons was higher and CD4 cell counts lower when this allele contributed to the overall CD8 + T cell response, which was detected exclusively through a single epitope in Env. In addition, persons heterozygous for B*5802 compared to persons homozygous for other HLA-B alleles had significantly higher viral loads. Viral sequencing revealed strong selection pressure mediated through B*5801-restricted responses but not through B*5802. These data indicate that minor differences in HLA sequence can have a major impact on epitope recognition, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia. These results provide experimental evidence that not all epitope-specific responses contribute to immune containment, a better understanding of which is essential to shed light on mechanisms involved in HIV disease progression. © 2008 Mary Ann Liebert, Inc.
Authors & Co-Authors
Ngumbela, Kholiswa C.
South Africa, Durban
The Nelson R. Mandela Medical School
Day, Cheryl Cheryl L.
South Africa, Durban
The Nelson R. Mandela Medical School
United States, Boston
Massachusetts General Hospital
Mncube, Zenele
South Africa, Durban
The Nelson R. Mandela Medical School
Nair, Kriebashnie S.
South Africa, Durban
The Nelson R. Mandela Medical School
Ramduth, Danni
South Africa, Durban
The Nelson R. Mandela Medical School
Thobakgale, Christina F.
South Africa, Durban
The Nelson R. Mandela Medical School
Moodley, Eshia S.
South Africa, Durban
The Nelson R. Mandela Medical School
Reddy, Sharon
South Africa, Durban
The Nelson R. Mandela Medical School
de Pierres, Chantal
South Africa, Durban
The Nelson R. Mandela Medical School
Mkhwanazi, Nompumelelo Prudence
South Africa, Durban
The Nelson R. Mandela Medical School
Bishop, Karen S.
South Africa, Durban
The Nelson R. Mandela Medical School
van der Stok, Mary
South Africa, Durban
The Nelson R. Mandela Medical School
Ismail, Nasreen
South Africa, Durban
The Nelson R. Mandela Medical School
Honeyborne, Isobella
South Africa, Durban
The Nelson R. Mandela Medical School
United Kingdom, Oxford
Nuffield Department of Medicine
Crawford, Hayley
United Kingdom, Oxford
Nuffield Department of Medicine
Kavanagh, Daniel G.
United States, Boston
Massachusetts General Hospital
Rousseau, Christine M.
United States, Seattle
University of Washington
Nickle, David C.
United States, Seattle
University of Washington
Mullins, James I.
United States, Seattle
University of Washington
Heckerman, David E.
United States, Redmond
Microsoft Research
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
United States, Santa fe
Santa fe Institute
Coovadia, Hoosen Mahomed
South Africa, Durban
The Nelson R. Mandela Medical School
Kiepiela, Photini
South Africa, Durban
The Nelson R. Mandela Medical School
Goulder, Philip Jeremy Renshaw
South Africa, Durban
The Nelson R. Mandela Medical School
United States, Boston
Massachusetts General Hospital
United Kingdom, Oxford
Nuffield Department of Medicine
Walker, Bruce D.
South Africa, Durban
The Nelson R. Mandela Medical School
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Statistics
Citations: 76
Authors: 25
Affiliations: 8
Identifiers
Doi:
10.1089/aid.2007.0124
ISSN:
08892229
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study