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bioRxiv · 10.1101/2021.03.28.437363

SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response

Xiao, C.·Mao, L.·Wang, Z.·Zhu, G.·Gao, L.·Su, J.·Chen, X.·Yuan, J.·Hu, Y.·Luo, O. J.·Wang, P.·Chen, G.
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Abstract

The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8+ T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8+ T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8+ T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8+ T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8+ T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8+ T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238. Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8+ T cell responses elicited by infection of mutated strains or vaccination. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/437363v2_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@b9f2cdorg.highwire.dtl.DTLVardef@1f39e3dorg.highwire.dtl.DTLVardef@119c313org.highwire.dtl.DTLVardef@565388_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Xiao, C., Mao, L., Wang, Z., Zhu, G., Gao, L., Su, J., Chen, X., Yuan, J., Hu, Y., Luo, O. J., Wang, P., Chen, G.. 2021-03-29. SARS-CoV-2 variant B.1.1.7 caused HLA-A2+ CD8+ T cell epitope mutations for impaired cellular immune response. https://doi.org/10.1101/2021.03.28.437363

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