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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.

Original publication

DOI

10.1016/j.celrep.2021.109103

Type

Journal article

Journal

Cell reports

Publication Date

05/2021

Volume

35

Addresses

Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK; National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, Oxford OX4 2PG, UK; Research In Viral Eradication of Reservoirs (RIVER) trial study group. Electronic address: hongbing.yang@ndm.ox.ac.uk.

Keywords

Research in Viral Eradication of Reservoirs (RIVER) trial study group