Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Nat Commun. 2018 Nov 27;9(1):5023. doi: 10.1038/s41467-018-07209-7.


Some closely related human leukocyte antigen (HLA) alleles are associated with variable clinical outcomes following HIV-1 infection despite presenting the same viral epitopes. Mechanisms underlying these differences remain unclear but may be due to intrinsic characteristics of the HLA alleles or responding T cell repertoires. Here we examine CD8+ T cell responses against the immunodominant HIV-1 Gag epitope TL9 (TPQDLNTML180-188) in the context of the protective allele B*81:01 and the less protective allele B*42:01. We observe a population of dual-reactive T cells that recognize TL9 presented by both B*81:01 and B*42:01 in individuals lacking one allele. The presence of dual-reactive T cells is associated with lower plasma viremia, suggesting a clinical benefit. In B*42:01 expressing individuals, the dual-reactive phenotype defines public T cell receptor (TCR) clones that recognize a wider range of TL9 escape variants, consistent with enhanced control of viral infection through containment of HIV-1 sequence adaptation.

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • CD8-Positive T-Lymphocytes / immunology
  • Clone Cells
  • Female
  • HIV-1 / metabolism*
  • HLA-B Antigens / immunology*
  • Humans
  • Male
  • Mutation / genetics*
  • Receptors, Antigen, T-Cell / metabolism*
  • Reproducibility of Results
  • Viral Load
  • Young Adult
  • gag Gene Products, Human Immunodeficiency Virus / chemistry
  • gag Gene Products, Human Immunodeficiency Virus / genetics*


  • HLA-B Antigens
  • Receptors, Antigen, T-Cell
  • gag Gene Products, Human Immunodeficiency Virus