Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses

Cell Rep. 2021 May 11;35(6):109103. doi: 10.1016/j.celrep.2021.109103.

Abstract

Persistence of HIV through integration into host DNA in CD4+ T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8+ T cells are triggered to kill infected CD4+ T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial" HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A∗02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8+ T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4+ T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.

Keywords: CD8 T cells; Gag; HIV; HLA; antigen presentation; cytotoxic T lymphocytes; immunopeptidome; kinetics; mass spectrometry; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology*
  • HIV Infections / immunology*
  • Humans
  • Peptides / metabolism*
  • Virion / immunology*

Substances

  • Antiviral Agents
  • Peptides