HIV-1 NEF ligands predominate in the HLA class I of infected CD4+ T cells (APP2P.108)

Abstract

Abstract Class I HLA reveal virus-derived ligands to cytotoxic T lymphocytes (CTL) whose function is to eliminate infected cells. The Los Alamos National Laboratory (LANL) database reports numerous HIV-1 CTL epitopes, none of which have elicited protective immunity in vaccine testing. The goal of this study was to determine the number and nature of HIV-1 ligands available for CTL targeting through presentation by the HLA class I of virus-infected cells. Class I presented peptides were recovered from immunoaffinity purified HLA-A*11:01 gathered from HIV-1 (NL4-3)-infected human CD4+ SUP-T1 T cells. These peptides were fractionated by RP-HPLC and mapped by tandem mass spectrometry (MS/MS). Seven HIV-derived peptides were confirmed by MS/MS as unique to infected cells. Twelve LANL HIV epitopes, including the well-studied Gag p24 epitope ACQGVGGPGHK (AK11), were clearly absent from the HLA-A*11:01 of infected cells. Of the 7 HIV-1 ligands found to be presented by A*11:01, 4 were derived from Nef, 2 from Gag, and 1 from Pol. When these 7 ligands were tested for T cell reactivity in a gamma interferon ELISPOT assay using PBMC from HIV-1 infected individuals (including elite controllers), the Nef-derived peptides were found to be highly reactive. These data demonstrate that the class I HLA of HIV-1 infected CD4+ T cells present a handful of viral peptide ligands for recognition by CTL and that reported HIV-1 CTL epitopes might not be presented by the HLA class I of infected cells.