Adaptive interactions between HLA and HIV-1: highly divergent selection imposed by HLA class I molecules with common supertype motifs.

TitleAdaptive interactions between HLA and HIV-1: highly divergent selection imposed by HLA class I molecules with common supertype motifs.
Publication TypeJournal Article
Year of Publication2010
AuthorsJohn M, Heckerman D, James I, Park LP, Carlson JM, Chopra A, Gaudieri S, Nolan D, Haas DW, Riddler SA, Haubrich R, Mallal S
JournalJ Immunol
Volume184
Issue8
Pagination4368-77
Date Published2010 Apr 15
ISSN1550-6606
KeywordsAdaptive Immunity, Amino Acid Motifs, Cohort Studies, Genetic Variation, Genotype, Histocompatibility Antigens Class I, Histocompatibility Testing, HIV Infections, HIV-1, HLA Antigens, Humans, Molecular Sequence Data, Peptides, Polymorphism, Genetic, Protein Binding, Randomized Controlled Trials as Topic, Receptors, Antigen, T-Cell, United States, Western Australia
Abstract

Currently, 1.1 million individuals in the United States are living with HIV-1 infection. Although this is a relatively small proportion of the global pandemic, the remarkable mix of ancestries in the United States, drawn together over the past two centuries of continuous population migrations, provides an important and unique perspective on adaptive interactions between HIV-1 and human genetic diversity. HIV-1 is a rapidly adaptable organism and mutates within or near immune epitopes that are determined by the HLA class I genotype of the infected host. We characterized HLA-associated polymorphisms across the full HIV-1 proteome in a large, ethnically diverse national United States cohort of HIV-1-infected individuals. We found a striking divergence in the immunoselection patterns associated with HLA variants that have very similar or identical peptide-binding specificities but are differentially distributed among racial/ethnic groups. Although their similarity in peptide binding functionally clusters these HLA variants into supertypes, their differences at sites within the peptide-binding groove contribute to race-specific selection effects on circulating HIV-1 viruses. This suggests that the interactions between the HLA/HIV peptide complex and the TCR vary significantly within HLA supertype groups, which, in turn, influences HIV-1 evolution.

DOI10.4049/jimmunol.0903745
Alternate JournalJ. Immunol.
PubMed ID20231689
PubMed Central IDPMC3011274
Grant ListAI046376 / AI / NIAID NIH HHS / United States
AI069419 / AI / NIAID NIH HHS / United States
AI069424 / AI / NIAID NIH HHS / United States
AI069432 / AI / NIAID NIH HHS / United States
AI069434 / AI / NIAID NIH HHS / United States
AI069439 / AI / NIAID NIH HHS / United States
AI069447 / AI / NIAID NIH HHS / United States
AI069450 / AI / NIAID NIH HHS / United States
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AI069471 / AI / NIAID NIH HHS / United States
AI069472 / AI / NIAID NIH HHS / United States
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AI069501 / AI / NIAID NIH HHS / United States
AI069502 / AI / NIAID NIH HHS / United States
AI069513 / AI / NIAID NIH HHS / United States
AI069532 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
AI25859 / AI / NIAID NIH HHS / United States
AI27661 / AI / NIAID NIH HHS / United States
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AI38858 / AI / NIAID NIH HHS / United States
AI46370 / AI / NIAID NIH HHS / United States
AI64086 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
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AI69423 / AI / NIAID NIH HHS / United States
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AI69494 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-05 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
R01 AI060460 / AI / NIAID NIH HHS / United States
R01 AI060460 / AI / NIAID NIH HHS / United States
R01 AI060460-01 / AI / NIAID NIH HHS / United States
RR024975 / RR / NCRR NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States