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

作者：Yu Xu G; Lichterfeld Mathias; Chetty Senica; Williams Katie L; Mui Stanley K; Miura Toshiyuki; Frahm Nicole; Feeney Margaret E; Tang Yanhua; Pereyra Florencia; LaBute Montiago X; Pfafferott Katja; Leslie Alisdair; Crawford Hayley; Allgaier Rachel; Hildebrand William; Kaslow Richard; Brander Christian; Allen Todd M; Rosenberg Eric S; Kiepiela Photini; Vajpayee Madhu; Goepfert Paul A; Altfeld Marcus; Goulder Philip J R; Walker Bruce D^*

来源：Journal of Virology, 2007, 81(4): 1619-1631.

DOI：10.1128/JVI.01580-06

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 (KAFSPEVIP MF). When this epitope is presented by HLA-13*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 HIA-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.

• 出版日期2007-2
• 单位河北医科大学