Identification and characterization of a SARS-CoV-2 specific CD8(+) T cell response with immunodominant features

Gangaev, A.; Ketelaars, S.L.C.; Isaeva, O.I.; Patiwael, S.; Dopler, A.; Hoefakker, K.; Biasi, S. de; Gibellini, L.; Mussini, C.; Guaraldi, G.; Girardis, M.; Ormeno, C.M.P.T.; Hekking, P.J.M.; Lardy, N.M.; Toebes, M.; Balderas, R.; Schumacher, T.N.; Ovaa, H.; Cossarizza, A.; Kvistborg, P.

doi:doi:10.1038/s41467-021-22811-y

Many viral antigens have been identified in patients with COVID-19 patients, but which of these result in meaningful immune responses is unclear. Here the authors identify a range of SARS-CoV-2 CD8(+) T cell responses across patients including a response targeting an epitope of ORF1ab with immunodominant properties.The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8(+) T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8(+) T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8(+) T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8(+) T cell responses of patients with acute critical and severe disease reveals high expression of...Show moreMany viral antigens have been identified in patients with COVID-19 patients, but which of these result in meaningful immune responses is unclear. Here the authors identify a range of SARS-CoV-2 CD8(+) T cell responses across patients including a response targeting an epitope of ORF1ab with immunodominant properties.The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8(+) T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8(+) T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8(+) T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8(+) T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8(+) T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8(+) T cells during convalescence.Show less

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Identification and characterization of a SARS-CoV-2 specific CD8(+) T cell response with immunodominant features