SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Abstract

Understanding the hallmarks of the adaptive immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed the antibody and T-cell reactivity in COVID-19 convalescent patients and healthy donors sampled both prior to and during the pandemic. The numbers of SARS- CoV-2-specific T cells were increased in healthy donors examined during COVID-19. Combined with the absence of symptoms and humoral response across that group, this finding suggests that some individuals might be protected by T-cell cross-reactivity. In convalescent patients we observed public and diverse T-cell response to SARS-CoV-2 epitopes, revealing T-cell receptor motifs with germline- encoded features. Bulk CD4+ and CD8+ T-cell responses to Spike glycoprotein were mediated by groups of homologous T-cell receptors, some of them shared across multiple donors. Overall, our results demonstrate that T-cell response to SARS-CoV-2, including the identified set of specific T-cell receptors, can serve as a useful biomarker for surveying viral exposure and immunity.

Identification and characterization of an immunodominant SARS-CoV-2-specific CD8 T cell response

“…Accumulating information on the antibody response against SARS-CoV-2 demonstrates that structural proteins such as the spike and nucleoprotein serve as potent antibody targets in a substantial fraction of COVID-19 patients [2][3][4][5][6] . However, much less is currently known regarding the SARS-CoV-2-speci c T cell response, in particular which parts of the virus are targeted by T cells.…”

“…However, accumulating data provide evidence for a broader repertoire of the SARS-CoV-2 derived T cell antigens 6-9,11,12. The vast majority of studies demonstrating T cell reactivity against SARS-CoV-2 are based on large peptide pools [7][8][9]12,13 . Only few studies have identi ed exact T cell epitopes and their restriction elements, and these have mainly been focused on HLA-A*02:01 and a limited set of selected epitopes from the spike protein 2,6,10 . Therefore, broader efforts are needed to provide fundamental insights into which parts of the SARS-CoV-2 proteome induce potent CD8 T cell responses.…”

COVIDep platform for real-time reporting of vaccine target recommendations for SARS-CoV-2: Description and connections with COVID-19 immune responses and preclinical vaccine trials

“…Conversely, studies have demonstrated that specific SARS-CoV-derived antibodies binding to the spike's receptor binding domain, which has significant genetic differences in SARS-CoV-2, have limited cross-reactivity 7 . Antibody and T cell responses against spike protein epitopes that are genetically similar in SARS-CoV and SARS-CoV-2 have also been reported in COVID-19 infected patients [8][9][10] , and in preclinical vaccine trials 11,12 . Epitopes recommended by COVIDep have notable overlap with the findings in these experimental studies (Figures 2 and 3).…”

“…The epitopes with IEDB IDs 52020 and 16183 overlap with the regions reported to be recognized by neutralizing antibodies in the sera of recovered COVID-19 patients 8 . 9,10 . In a preclinical vaccine trial 12 , T cell responses have also been recorded against a protein region comprising the identified epitope with IEDB ID 71663.…”

“…The specific overlapping residues are underlined, with double-underline reflecting that a response was observed in two studies. A more prominent underline is used to distinguish the epitope with IEDB ID 54725, since a response against this epitope was observed in ten COVID-19 patients (of fourteen studied) 10 . The epitopes with IEDB IDs 36724, 69657, 71663, 2801, 54680, and 16156 were originally reported based on positive T cell assays for SARS-CoV, while those with IEDB IDs 54507, 54725, and 37289 were reported based on positive MHC binding assays.…”