Poster Presentation 12th Australasian Virology Society Meeting 2024

Further insights into asymptomatic outcome after SARS-CoV-2 in HLA-B*15:01+ individuals (#215)

Lawton L.M Murdolo 1 2 , Janesha J.M Maddumage 1 2 , Dimitra D.C Chatzileontiadou 1 2 , Stephanie S.G Gras 1 2
  1. Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia
  2. Infection and Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia

T lymphocyte activation is driven by the recognition of Human Leukocyte Antigens (HLA) on the surface infected cells. HLAs present viral peptides to T cells, which then recognize them as antigens via their T cell receptor (TCR). Our previous work showed a specific HLA-B*15:01 can present a SARS-CoV-2 (NQK-Q8) and a seasonal coronavirus peptide (NQK-A8) in the same conformation, with the same thermal stability. We then show these peptides illicit a similar T cell response, driven by high affinity binding of identical TCRs, found in different HLA-B*15:01+ individuals1..

To further investigate this result, I used X-ray crystallography to show theses TCRs only contact three residues on each peptide. With this interaction driven prominently by the HLA alone. Therefore, to determine if changes to the peptide effect conformation, stability and TCR recognition, I determined the crystal structures, thermal stabilities, and binding affinities of HLA-B*15:01, presenting different peptides with mutations and self-derived peptides.

I show that a single mutation causes substantial change in the peptide presentation, which in turn limits binding affinity and reduces T cell activation. This highlights the importance of theses side chains which play a critical role in providing protection against SARS-CoV-2 within HLA-B*15:01+ individuals

  1. 1.Augusto, D.G., Murdolo, L.D., Chatzileontiadou, D.S.M. et al. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Nature 620, 128–136 (2023). https://doi.org/10.1038/s41586-023-06331-x