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

Journal article

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.

Authors: Yang, H; Llano, A; Cedeño, S; von Delft, A; Corcuera, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell Reports
• Volume: 35
• Issue: 6
• Article number: 109103
• Publication date: 2021-05-11
• Acceptance date: 2021-04-16
• DOI: 10.1016/j.celrep.2021.109103
• ISSN: 2211-1247
• Pmid: 33979627
• Language: English
• Keywords: immunopeptidome; peptides; HIV; cytotoxic T lymphocytes; antigen presentation; FFR; CD8 T cells; kinetics; mass spectrometry; Gag; HLA