Department of Pathology; Department of Medicine; Department of Biochemistry and Molecular Biotechnology; Graduate School of Biomedical Sciences
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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DOI of Published Version
bioRxiv 2022.01.20.477107; doi: https://doi.org/10.1101/2022.01.20.477107. Link to preprint on bioRxiv.
Now published in Cell Reports doi: 10.1016/j.celrep.2022.110952
Becerra-Artiles A, Calvo-Calle JM, Co MT, Nanaware PP, Cruz J, Weaver GC, Lu L, Forconi C, Finberg RW, Moormann AM, Stern LJ. (2022). Broadly-recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2022.01.20.477107. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2215
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