Direct identification of HLA-presented CD8 T cell epitopes from transmitted founder HIV-1 variants

Proteomics. 2021 Sep;21(17-18):e2100142. doi: 10.1002/pmic.202100142. Epub 2021 Aug 1.


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.

Keywords: biomedicine; immunoproteomics; infectious diseases; mass spectrometry-LC-MS/MS; technology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Epitopes, T-Lymphocyte
  • HIV-1*
  • Leukocytes, Mononuclear
  • Tandem Mass Spectrometry


  • Epitopes, T-Lymphocyte