UMass Chan Medical School Faculty Publications

UMMS Affiliation

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

Publication Date

2022-01-22

Document Type

Article Preprint

Disciplines

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

Abstract

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.

Keywords

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

Rights and Permissions

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

DOI of Published Version

10.1101/2022.01.20.477107

Source

bioRxiv 2022.01.20.477107; doi: https://doi.org/10.1101/2022.01.20.477107. Link to preprint on bioRxiv.

Comments

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 Preprints are preliminary reports of work that have not been certified by peer review.

Related Resources

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

Journal/Book/Conference Title

bioRxiv

Creative Commons License

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.

Share

COinS