Oral Presentation 22nd Annual Lorne Proteomics Symposium 2017

An immunoproteomics approach for the identification of novel influenza B T cell epitopes. (#11)

Patricia Illing 1 , Marios Koutsakos 2 , Nicole Mifsud 1 , Bridie Clemens 2 , Oanh Nguyen 2 , Katherine Kedzierska 2 , Anthony Purcell 1
  1. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  2. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia

Although influenza B viruses (IBVs) can contribute over 50% of seasonal influenza infections and cause severe respiratory disease, investigations of T cell responses to influenza have largely focussed on influenza A viruses (IAVs). To date only a handful of IBV derived T cell epitopes have been identified, primarily through epitope prediction or homology to IAV. Here we used mass spectrometry for unbiased identification of IBV peptides presented by HLA class I and II molecules for functional investigation. We infected human B-lymphoblastoid cell lines with IBV and  sequentially immunoaffinity purified HLA-peptide complexes to yield peptides bound to (1) the common Caucasian class I allotype HLA-A*02:01, (2) the remaining class I allotypes HLA-C*04:01 and B*35:03, and (3) the class II HLA molecules (HLA-DRB1*12:01, DRB3*02:02, DQB1*03:01 and DPB1*04:01) of these cells. Eluted peptide ligands were analysed by LC-MS/MS. We identified 71 HLA class I ligands of 8-13 residues length which spanned all proteins in the IBV proteome, except the ion channel BM2 (10/11 proteins). Of these, 58 were assigned as HLA-A*02:01 ligands, commonly displaying hydrophobic HLA-A*02:01 anchor residues at P2 and the C-terminus, and 4 as HLA-C*04:01 ligands, predominantly bearing aromatic or aliphatic residues at P2 and the C-terminus, and Asp at P3. A further 212 HLA class II ligands, principally 12-18 residues in length, were identified from 6/11 IBV proteins. Notably, although dominated by hemagglutinin, HLA class II ligands were also sourced from BM2, suggesting compartmentalisation to the HLA class II loading pathway. Preliminary functional analyses in HLA-A*02:01+ individuals and HLA-A*02:01 transgenic mice determined the immunogenicity of a number of the HLA-A*02:01 IBV derived peptide ligands identified, confirming the potential of this approach to provide candidate peptides for investigation of IBV-specific T cell responses.