Direct identification of HLA-presented CD8 T cell epitopes from transmitted founder HIV-1 variants.
Jonathan HareGladys MachariaLing YueClaire L StreatfieldEric HunterAnthony Wayne PurcellNicola TernetteJill GilmourPublished in: Proteomics (2021)
Cytotoxic T lymphocytes (CTLs) are a critical arm of the immune response to viral infections. The activation and expansion of antigen specific CTL requires recognition of peptide antigens presented on class I major histocompatibility complex molecules (MHC-1) of infected cells. Methods to identify presented peptide antigens that do not rely on the pre-existence of antigen specific CTL are critical to the development of new vaccines. We infected activated CD4+ T cells with two HIV-1 transmitted founder (TF) isolates and used high-resolution mass spectrometry (MS) to identify HIV peptides bound on MHC-1. Using this approach, we identified 14 MHC-1 bound peptides from across the two TF isolates. Assessment of predicted binding thresholds revealed good association of the identified peptides to the shared HLA alleles between the HIV+ donors and the naïve PBMC sample with three peptides identified through peptide sequencing inducing a CD8 T-cell response (p < 0.05). Direct infection of naïve CD4 cells by HIV TF isolates and sequencing of MHC-I presented peptides by HPLC-MS/MS enables identification of novel peptides that may be missed by alternative epitope mapping strategies and can provide valuable insight in to the first peptides presented by an HIV-infected CD4 cell in the first few days post infection.
Keyphrases
- hiv infected
- antiretroviral therapy
- hiv positive
- human immunodeficiency virus
- hiv testing
- ms ms
- hiv aids
- hepatitis c virus
- men who have sex with men
- amino acid
- single cell
- induced apoptosis
- mass spectrometry
- south africa
- high resolution mass spectrometry
- cell cycle arrest
- high resolution
- immune response
- dendritic cells
- dna methylation
- mesenchymal stem cells
- cell proliferation
- stem cells
- liquid chromatography
- signaling pathway
- oxidative stress
- high performance liquid chromatography