Broadly-recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles [preprint]
Authors
Becerra-Artiles, AniuskaCalvo-Calle, J. Mauricio
Co, Mary Dawn T.
Nanaware, Padma P.
Cruz, John
Weaver, Grant
Lu, Liying
Forconi, Catherine S
Finberg, Robert W.
Moormann, Ann M.
Stern, Lawrence J.
UMass Chan Affiliations
Graduate School of Biomedical SciencesDepartment of Biochemistry and Molecular Biotechnology
Department of Medicine
Department of Pathology
Document Type
PreprintPublication Date
2022-01-22Keywords
Heterologous immunitySARS-CoV-2
common-cold coronavirus
COVID-19
T cell receptor
Major Histocompatibility Complex
Spike fusion peptide proximal region
CD4+ T cell
TCR clonotype
Amino Acids, Peptides, and Proteins
Immunology and Infectious Disease
Microbiology
Virus Diseases
Metadata
Show full item recordAbstract
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.Source
bioRxiv 2022.01.20.477107; doi: https://doi.org/10.1101/2022.01.20.477107. Link to preprint on bioRxiv.
DOI
10.1101/2022.01.20.477107Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30744Notes
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 Preprints are preliminary reports of work that have not been certified by peer review.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.2022.110952Rights
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.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/2022.01.20.477107
Scopus Count
Except where otherwise noted, this item's license is described as 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.