Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8+ T cell antiviral responses
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 peptide...
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Veröffentlicht in: | Cell reports (Cambridge) 2021-05, Vol.35 (6), p.109103-109103, Article 109103 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•CD8+ T cell recognition of incoming HIV antigens leads to efficient virus control•HLA-I-bound HIV peptides from incoming virions are identifiable by mass spectrometry•Gag Spacer Peptide 2 elicits killing of CD4+ T cells early in the viral life cycle•Early CD8+ T cell killing is not dependent on protective HLA class I alleles
Unbiased approaches to deciphering immune control mechanisms in people with HIV may help in the search for a cure. Yang et al. use proteomics to identify viral peptides presented early in the viral life cycle and show that Gag Spacer Peptide 2 recognition triggers efficient CD8+ T cell killing. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2021.109103 |