UMass Chan Medical School Faculty Publications

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Department of Pathology; Department of Medicine; Department of Biochemistry and Molecular Biotechnology; Graduate School of Biomedical Sciences

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Article Preprint


Amino Acids, Peptides, and Proteins | Immunology and Infectious Disease | Microbiology | Virus Diseases


Sequence homology between SARS-CoV-2 and common-cold human coronaviruses (HCoVs) raises the possibility that memory responses to prior HCoV infection can impact the T cell response in COVID-19. We studied T cells recognizing SARS-CoV-2 and HCoVs in convalescent COVID-19 donors, and identified a highly conserved SARS-CoV-2 sequence S811-831, with two overlapping epitopes presented by common MHC-II proteins HLA-DQ5 and HLA-DP4. These epitopes were recognized by CD4+ T cells from convalescent COVID-19 donors, mRNA vaccine recipients, and by low-abundance CD4+ T cells in uninfected donors. TCR sequencing revealed a diverse repertoire with public TCRs. CD4+ T cell cross-reactivity was driven by the remarkably strong conservation of T cell contact residues in both HLA-DQ5 and HLA-DP4 binding frames, with distinct patterns of HCoV cross-reactivity explained by MHC-II binding preferences and substitutions at secondary TCR contact sites. These data highlight S811-831 as a highly-conserved CD4+ T cell epitope broadly recognized across human populations.


Heterologous immunity, SARS-CoV-2, common-cold coronavirus, COVID-19, T cell receptor, Major Histocompatibility Complex, Spike fusion peptide proximal region, CD4+ T cell, TCR clonotype

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bioRxiv 2022.01.20.477107; doi: Link to preprint on bioRxiv.


This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

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Now published in Cell Reports doi: 10.1016/j.celrep.2022.110952

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Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.