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.

Journal article

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.

Authors: Yu, X; Lichterfeld, M; Chetty, S; Williams, K; Mui, S

• Publication status: Published
• Journal: Journal of virology
• Volume: 81
• Issue: 4
• Pages: 1619-1631
• Publication date: 2007-02-01
• DOI: 10.1128/jvi.01580-06
• EISSN: 1098-5514
• ISSN: 0022-538X
• Language: English
• Keywords: Species Specificity; Histocompatibility Antigens Class I; Immunodominant Epitopes; HIV-1; Receptors, Antigen, T-Cell; Alleles; Epitopes, T-Lymphocyte; CD8-Positive T-Lymphocytes; Gene Products, gag; Mutation; Amino Acid Substitution; HIV Infections; Humans