CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2

Qiu, C.; Xiao, C.; Wang, Z.; Zhu, G.; Chen, X.; Gao, L.; Den, J.; Su, J.; Su, H.; Fang, E. F.; Zhang, Z.; Zhang, J.; Luo, O. J.; Wang, P.; Chen, G.

doi:10.1101/2021.01.22.427863

bioRxiv · 10.1101/2021.01.22.427863

CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2

Qiu, C.·Xiao, C.·Wang, Z.·Zhu, G.·Chen, X.·Gao, L.·Den, J.·Su, J.·Su, H.·Fang, E. F.·Zhang, Z.·Zhang, J.·Luo, O. J.·Wang, P.·Chen, G.

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Abstract

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation 5L>F significantly decreased the proportion of specific T cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.

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Qiu, C., Xiao, C., Wang, Z., Zhu, G., Chen, X., Gao, L., Den, J., Su, J., Su, H., Fang, E. F., Zhang, Z., Zhang, J., Luo, O. J., Wang, P., Chen, G.. 2021-01-24. CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2. https://doi.org/10.1101/2021.01.22.427863

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