The adaptive immune system is distributed into two main arms, cellular and humoral immunity. Cytotoxic CD8+T cells, from the cellular arm, are activated in three steps: antigen recognition, co-stimulation and cytokine stimulation. CD8+ T cells recognises small viral peptides bound by Human Leukocyte Antigen class I (HLA) molecules on the surface of all nucleated cells. The three HLA of interest, expressed in a 1/3 of the global population, are HLA-A*11:01, HLA-B*13:01 and HLA-A*02:01.
SARS-CoV-2 has infected millions across the global population, resulting in millions of deaths. SARS-CoV-2 is a positive-sense single-stranded RNA virus that is surrounded by four viral proteins: Nucleocapsid (N), Membrane (M), Envelope (E) and Spike (S). Current vaccines encode mainly for the Spike to produce neutralising antibody response. A region of the Spike containing the S975-984 (SVLNDILSRL, Wuhan strain) peptide, has mutated (underlined) into two Variants of Concerns (VoCs), Alpha (SVLNDILARL) and Omicron BA.1 (SVLNDIFSRL).
In this project, crystal structures of HLA-A*11:01 presenting the three S975-984 peptides (from Wuhan, Alpha and Omicron BA.1) and HLA-B*13:01 presenting two VoC peptides were solved and analysed. Stability assays showed the impact of the mutations on peptide presentation. Immunogenicity and T cell cross-reactivity between the peptides were assessed and analysed from samples isolated from vaccinated individuals and showed that the S975-984 peptide is weakly immunogenic.
Future research describing epitopes restricted to other frequently expressed HLA will assist in providing thorough protection for the global population. The immune responses against these peptides should not be overlooked as this could help understand the nature of future mutations.