Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients

Through single-cell TCR and RNA sequencing, the authors identified public cTfh clonotypes expanded in recovered COVID-19 patients and determined their epitopes in the specific regions of spike protein conserved among emerging SARS-CoV-2 variants, which are candidates for booster antigens. Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4(+) T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.

Automated summary

Through single-cell TCR and RNA sequencing, researchers identified public cTfh clonotypes expanded in recovered COVID-19 patients, determined their epitopes in the conserved regions of spike protein, and found that these epitopes may be valuable candidates for booster antigens to enhance adaptive immunity against the virus.