Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases

Tarke, Alison; Sidney, John; Kidd, Conner K.; Dan, Jennifer M.; Ramirez, Sydney I.; Yu, Esther Dawen; Mateus, Jose; da Silva Antunes, Ricardo; Moore, Erin; Rubiro, Paul; Methot, Nils; Phillips, Elizabeth; Mallal, Simon; Frazier, April; Rawlings, Stephen A.; Greenbaum, Jason A.; Peters, Bjoern; Smith, Davey M.; Crotty, Shane; Weiskopf, Daniela; Grifoni, Alba; Sette, Alessandro

T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens, and precisely measure virus-specific CD4+ and CD8+ T cells, we study epitope-specific T cell responses of 99 convalescent COVID-19 cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of HLA alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells.