The Impact of SARS-CoV-2 Spike Mutation on Peptide Presentation is HLA Allomorph-Specific

31 Pages Posted: 29 Dec 2023

See all articles by You Min Ahn

You Min Ahn

La Trobe University

Janesha C. Maddumage

La Trobe University

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology

Demetra S.M. Chatzileontiadou

La Trobe University - Department of Biochemistry & Chemistry

Christopher Szeto

La Trobe University - Department of Biochemistry & Chemistry

Stephanie Gras

La Trobe University - Department of Biochemistry & Chemistry

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 (S976-984, 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 S976-984. We identified a longer and overlapping immunogenic peptide (S975-984, 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 in 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.

Note:
Funding Information: This work was supported by the Medical Research Future Fund (MRFF, awarded to S.G.), AINSE grants (awarded to D.S.M.C. and E.J.G.); an ARC DECRA (awarded to E.J.G DE210101479) and an NHMRC SRF (awarded to S.G. grant number #11592720). Research Training Program (RTP) stipend scholarship (You Min Ahn).

Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics Approval Statement: All work using human samples was approved by the La Trobe University Human Ethics Committee (Approval No: HEC21097). Whole blood donations were received from healthy volunteers. All donors provided written and informed consent on the day of their donation.

Keywords: X-ray crystallography, SARS-CoV-2, T cells, viral epitopes, HLA, viral mutation

Suggested Citation

Ahn, You Min and Maddumage, Janesha C. and Grant, Emma J. and Chatzileontiadou, Demetra S.M. and Szeto, Christopher and Gras, Stephanie, The Impact of SARS-CoV-2 Spike Mutation on Peptide Presentation is HLA Allomorph-Specific. Available at SSRN: https://ssrn.com/abstract=4675838 or http://dx.doi.org/10.2139/ssrn.4675838

You Min Ahn

La Trobe University ( email )

Janesha C. Maddumage

La Trobe University ( email )

Emma J. Grant

Monash University - Department of Biochemistry and Molecular Biology ( email )

Clayton, Victoria
Australia

Demetra S.M. Chatzileontiadou

La Trobe University - Department of Biochemistry & Chemistry ( email )

Christopher Szeto

La Trobe University - Department of Biochemistry & Chemistry ( email )

Stephanie Gras (Contact Author)

La Trobe University - Department of Biochemistry & Chemistry ( email )

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