Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes.

TitleMutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes.
Publication TypePublication
Year of Publication2007
AuthorsYu XG, Lichterfeld M, Chetty S, Williams KL, Mui SK, Miura T, Frahm N, Feeney ME, Tang Y, Pereyra F, Labute MX, Pfafferott K, Leslie A, Crawford H, Allgaier R, Hildebrand W, Kaslow R, Brander C, Allen TM, Rosenberg ES, Kiepiela P, Vajpayee M, Goepfert PA, Altfeld M, Goulder PJR, Walker BD
JournalJ Virol
Volume81
Issue4
Pagination1619-31
Date Published2007 Feb
ISSN0022-538X
KeywordsAlleles, Amino Acid Substitution, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Gene Products, gag, Histocompatibility Antigens Class I, HIV Infections, HIV-1, Humans, Immunodominant Epitopes, Mutation, Receptors, Antigen, T-Cell, Species Specificity
Abstract

<p>The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR beta-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703(+) individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.</p>

DOI10.1128/JVI.01580-06
Alternate JournalJ. Virol.
PubMed ID17121793
PubMed Central IDPMC1797559
Grant ListP30 AI060354 / AI / NIAID NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
U01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD40533 / HD / NICHD NIH HHS / United States