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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
HLA-B*57 micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control
Journal of Virology, Volume 86, No. 2, Year 2012
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Description
The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLAB*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8 + T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8 + T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8 + T-cell responses generated that can drive significant selection pressure on the virus. © 2012, American Society for Microbiology.
Authors & Co-Authors
Kløverpris, Henrik N.
United Kingdom, Oxford
University of Oxford
Stryhn, Anette
Denmark, Copenhagen
Københavns Universitet
Harndahl, Mikkel
Denmark, Copenhagen
Københavns Universitet
van der Stok, Mary
South Africa, Durban
University of Kwazulu-natal
Payne, Rebecca P.
United Kingdom, Oxford
University of Oxford
Matthews, Philippa C.
United Kingdom, Oxford
University of Oxford
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Riddell, Lynn A.
United Kingdom, Northampton
Northampton General Hospital
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Statistics
Citations: 83
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1128/JVI.06150-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study