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Cell Rep . Broadly recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by commo

tetano

Editor, Senior Moderator
Cell Rep


. 2022 May 27;110952.
doi: 10.1016/j.celrep.2022.110952. Online ahead of print.
Broadly recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles


Aniuska Becerra-Artiles[SUP] 1 [/SUP], J Mauricio Calvo-Calle[SUP] 1 [/SUP], Mary Dawn Co[SUP] 2 [/SUP], Padma P Nanaware[SUP] 1 [/SUP], John Cruz[SUP] 1 [/SUP], Grant C Weaver[SUP] 1 [/SUP], Liying Lu[SUP] 1 [/SUP], Catherine Forconi[SUP] 2 [/SUP], Robert W Finberg[SUP] 2 [/SUP], Ann M Moormann[SUP] 2 [/SUP], Lawrence J Stern[SUP] 3 [/SUP]



Affiliations

Abstract

Sequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can affect T cell response in COVID-19. We studied T cell responses to SARS-CoV-2 and HCoVs in convalescent COVID-19 donors and identified a highly conserved SARS-CoV-2 sequence, S[SUB]811-831[/SUB], with overlapping epitopes presented by common MHC class II proteins HLA-DQ5 and HLA-DP4. These epitopes are recognized by low-abundance CD4 T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. T cell cross-reactivity is driven by the high conservation across human and animal coronaviruses of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC class II binding preferences and substitutions at secondary TCR contact sites. These data highlight S[SUB]811-831[/SUB] as a highly conserved CD4 T cell epitope broadly recognized across human populations.

Keywords: CD4 T cells; CP: Immunology; CP: Microbiology; T cell receptor repertoire; heterologous immunity; major histocompatibility complex; seasonal coronavirus; spike fusion peptide proximal region.
 
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