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

J Virol. 2007 Feb;81(4):1619-31. doi: 10.1128/JVI.01580-06. Epub 2006 Nov 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes, T-Lymphocyte / genetics
  • Gene Products, gag / immunology
  • HIV Infections / immunology*
  • HIV-1 / genetics*
  • HIV-1 / immunology*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunodominant Epitopes / genetics
  • Mutation
  • Receptors, Antigen, T-Cell / genetics*
  • Species Specificity


  • Epitopes, T-Lymphocyte
  • Gene Products, gag
  • Histocompatibility Antigens Class I
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell