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

Academic Article

Abstract

  • 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, 1*5701 and 1*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-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 β-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.
  • Digital Object Identifier (doi)

    Author List

  • Yu XG; Lichterfeld M; Chetty S; Williams KL; Mui SK; Miura T; Frahm N; Feeney ME; Tang Y; Pereyra F
  • Start Page

  • 1619
  • End Page

  • 1631
  • Volume

  • 81
  • Issue

  • 4