Abstract
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, S 811-831 , 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 S 811-831 as a highly conserved CD4 T cell epitope broadly recognized across human populations.
Keywords: CD4 T cells; CP: Immunology; CP: Microbiology; T cell receptor repertoire; heterologous immunity; major histocompatibility complex; seasonal coronavirus; spike fusion peptide proximal region.
【저자키워드】 heterologous immunity, seasonal coronavirus, CP: Immunology, CP: Microbiology, CD4 T cells, T cell receptor repertoire, major histocompatibility complex, spike fusion peptide proximal region., 【초록키워드】 COVID-19, SARS-CoV-2, mRNA vaccine, Infection, CD4, cross-reactivity, Protein, T cell, donors, convalescent, preference, fusion peptide, epitope, TCR, T cell receptor, T cell response, Heterologous, Donor, binding, memory response, Contact, CD4 T cell, TCR sequencing, human populations, overlapping, recipients, residue, SARS-CoV-2 sequence, Substitution, homology, MHC class, TCRs, uninfected, Affect, highlight, raise, common-cold, human coronavirus, conserved, animal coronavirus, explained, driven by, proximal, 【제목키워드】 SARS-CoV-2, CD4, T cell epitope, cross-reactive, HLA allele, human coronavirus, conserved,