Poster Presentation 50th Lorne Proteins Conference 2025

Investigating T cell responses to a nested peptide (#150)

Georgia Dow 1 2 , Emma Grant 1 2 3 , Stephanie Gras 1 2 3
  1. Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia
  2. Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment (SABE), La Trobe University, Bundoora, Victoria, Australia
  3. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia

One important component of the adaptive immune response is the T cells, either “helper” CD4+ T cells and the “killer” CD8+ T cells. Activation of these T cells involves their T cell receptor (TCR) recognising peptides presented by Human Leukocyte Antigens (HLAs). During infection, pathogen derived proteins are degraded into peptides that can be presented by HLA molecules to T cells. Typically, CD4+ T cells recognise long peptides ( >11 residues) presented by HLA-II, while CD8+ T cells recognise shorter peptides (8-10 residues) presented by HLA-I molecules.

The concept of nested peptides, where a shorter CD8+ T cell peptide could be nested within a longer CD4+ T cell peptide, allows a single (long) peptide to activate both CD8+ and CD4+ T cells, and has been relatively understudied.

This project investigated this phenomenon using a longer 13 residues T cell peptide (PB1411-423) containing a shorter 9 residues known CD8+ T cell epitope (PB1413-421).

Using T cell activation assays, we confirmed that the long PB1411-423 is a novel immunogenic peptide which could be presented by multiple HLA-II allomorphs. Interestingly, the PB1413-421-specific T cells were expanded when the peptide was in the nested conformation in some donors, however a greater proportion of CD8+ T cell activation was observed when using the shorter peptide. We are currently working on determining the structure of both peptides presented by the both HLA to understand the similarity shared by the nested peptides.

 This suggests a potential influence of peptide processing on the outcome of the T cell response, highlighting an area for future investigation to enable the optimal design of nested peptide to be used in vaccines.