Deciphering T cell responses to a clonotype resolution during infection

抄録

Human T cell receptors (TCRs) develop an extremely diverse repertoire, among which the pathogen-specific T cells have high diversity and low frequency in homeostatic conditions. Single-cell–based TCR- and RNA-sequencing analyses enable us to acquire paired TCR sequences, together with the gene expression signature of these individual T cells; however, the throughput is limited. To identify clonotypes associated with SARS-CoV-2 defense, we filtered T cells by recall antigen stimulation followed by sorting of responded T cells, in addition to other layers of analyses, such as deep bulk TCR sequencing and public TCR sequence databases. From convalescent COVID-19 patients, we identified TCRs of public circulating follicular helper (cTfh) clonotypes that were significantly expanded in patients that have recovered from mild COVID-19 but not in severely affected patients. In SARS-CoV-2 vaccinees, we found that highly responsive cTfh cells were more abundant in donors with sustained anti-S antibody titer (sustainers) than those who had declined antibody titer (decliners) after the 2nd dose of vaccination. These T-cell clonotypes tend to recognize conserved epitopes, some of which could be presented on various HLAs and activate T cells in multiple donors. These high-resolution platforms could provide invaluable information for future vaccine development.