Shared CD8⁺ T cell receptors for SARS-CoV-2

Using a high-throughput approach, Snyder et al. profile clonally expanded SARS-CoV-2-specific CD8⁺ T cells both at the individual level, mapping T cell receptors (TCRs) to 545 predicted HLA class I-binding peptides in 61 acute and convalescent patients with COVID-19, and at the population level, decoding shared COVID-19-associated TCRs in 1,015 patients versus control subjects. In total, this preprint identifies 23,179 unique virus-specific TCRs spanning the entire SARS-CoV-2 proteome. Importantly, HLA haplotypes were found to determine both clonal breadth and depth of an individual’s virus-specific CD8⁺ T cell response. By applying a logistic regression classifier, the authors show that publicly shared CD8⁺ TCRs may be used as a potential biomarker of current and past SARS-CoV-2 infection at high specificity and sensitivity.