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

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

doi:10.1016/j.xcrm.2021.100204

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

Cell Rep Med. 2021 Feb 16;2(2):100204. doi: 10.1016/j.xcrm.2021.100204. Epub 2021 Jan 26.

Authors

Alison Tarke^{1

2}, John Sidney¹, Conner K Kidd¹, Jennifer M Dan^{1

3}, Sydney I Ramirez^{1

3}, Esther Dawen Yu¹, Jose Mateus¹, Ricardo da Silva Antunes¹, Erin Moore¹, Paul Rubiro¹, Nils Methot¹, Elizabeth Phillips⁴, Simon Mallal⁴, April Frazier¹, Stephen A Rawlings³, Jason A Greenbaum¹, Bjoern Peters^{1

3}, Davey M Smith³, Shane Crotty^{1

3}, Daniela Weiskopf¹, Alba Grifoni¹, Alessandro Sette^{1

3}

Affiliations

¹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
² Department of Internal Medicine and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa 16132, Italy.
³ Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
⁴ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia.

Abstract

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.

Keywords: CD4+T cells; CD8+ T cells; COVID-19; HLA; SARS-CoV-2; T cells; epitopes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Abstract

Publication types

Grants and funding