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,
J. Mauricio Calvo-Calle,
Mary Dawn Co,
Padma P. Nanaware,
John Cruz,
Grant C. Weaver,
Liying Lu,
Catherine Forconi,
Robert W. Finberg,
Ann M. Moormann,
Lawrence J. Stern
Affiliations
Aniuska Becerra-Artiles
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
J. Mauricio Calvo-Calle
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
Mary Dawn Co
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA
Padma P. Nanaware
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
John Cruz
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
Grant C. Weaver
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
Liying Lu
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA
Catherine Forconi
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA
Robert W. Finberg
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA
Ann M. Moormann
Department of Medicine, UMass Chan Medical School, Worcester, MA 01655, USA
Lawrence J. Stern
Department of Pathology, UMass Chan Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Biotechnology, UMass Chan Medical School, Worcester, MA 01655, USA; Corresponding author
Summary: 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, S811-831, 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 S811-831 as a highly conserved CD4 T cell epitope broadly recognized across human populations.
