The impact of SARS-CoV-2 spike mutation on peptide presentation is HLA allomorph-specific.

Curr Res Struct Biol

Infection & Immunity Program, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Bundoora, Victoria, Australia.

Published: April 2024

AI Article Synopsis

  • CD8 T cells play a key role in fighting viral infections, but there’s limited knowledge about their response to SARS-CoV-2 at the antigen level, particularly concerning the Spike protein's mutations.
  • Researchers studied an immunogenic peptide from the Spike protein that is affected by mutations in the Alpha and Omicron variants, finding that the Alpha mutation alters the peptide's stability and shape.
  • The study also discovered that a longer peptide can be presented by different HLA molecules, showing that T cells can weakly respond to mutant variants after vaccination, highlighting the importance of HLA specificity in immune responses.

Article Abstract

CD8 T cells are crucial for viral elimination and recovery from viral infection. Nonetheless, the current understanding of the T cell response to SARS-CoV-2 at the antigen level remains limited. The Spike protein is an external structural protein that is prone to mutations, threatening the efficacy of current vaccines. Therefore, we have characterised the immune response towards the immunogenic Spike-derived peptide (S, VLNDILSRL), restricted to the HLA-A*02:01 molecule, which is mutated in both Alpha (S982A) and Omicron BA.1 (L981F) variants of concern. We determined that the mutation in the Alpha variant (S982A) impacted both the stability and conformation of the peptide, bound to HLA-A*02:01, in comparison to the original S. We identified a longer and overlapping immunogenic peptide (S, SVLNDILSRL) that could be presented by HLA-A*02:01, HLA-A*11:01 and HLA-B*13:01 allomorphs. We showed that S975-specific CD8 T cells were weakly cross-reactive to the mutant peptides despite their similar conformations when presented by HLA-A*11:01. Altogether, our results show that the impact of SARS-CoV-2 mutations on peptide presentation is HLA allomorph-specific, and that post vaccination there are T cells able to react and cross-react towards the variant of concern peptides.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089313PMC
http://dx.doi.org/10.1016/j.crstbi.2024.100148DOI Listing

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