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

• Published in: Cell reports. Medicine Vol. 2; no. 2; p. 100204
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.02.2021; Elsevier
• Subjects: Advanced Basic Science; CD4+T cells; CD8+ T cells; COVID-19; epitopes; HLA; SARS-CoV-2; T cells; COVID-19; epitopes; SARS-CoV-2; CD4+T cells; CD8+ T cells; T cells; HLA
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100204

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 coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (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. [Display omitted] T cell responses recognize at least 30–40 epitopes in each donorImmunodominance is correlated with HLA bindingImmunodominant regions for CD4+ T cells have minimal overlap with antibody epitopesCD8+ T cell responses depend on the repertoire of HLA class I alleles Tarke et al. show a broad T cell repertoire, suggesting that viral escape of T cell immunity is unlikely. CD4 immunodominant regions correlate with HLA binding and not with high common cold coronavirus homology. RBD is poorly recognized by CD4s. Epitope pools can be used to optimize detection of T cell responses.