SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

Abstract

Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T-cell epitope data compiled from these studies, identifying 1400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity and for immune escape by SARS-CoV-2 variants.

HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses

“…Employing these two groups and sampling a set of healthy patients (n=12), we reveal the set of epitopes only recognised by public TCRs in these healthy patients, and those shared with the convalescent PubTCR-SharedEp group (Fig S5C, Supplementary Data File 3 and 4). Additionally, we reveal the peptides only observed in the PubTCR-Private convalescent group, adding to previous insights that SARS-CoV-2 infection can provoke T cell responses to a novel set of peptides compared to those expanded from unexposed patients 7 . Recent work shows cross-reactive private TCRs from unexposed subject repertoires, capable of recognising both the SARS-CoV-2 SPR* peptide and its LPR* homolog from HCoVs OC43 and HKU1.…”

“…More broadly, data are beginning to demonstrate distinct vaccine-induced responses linked to differential patient exposure to SARS-CoV-2 3,4 . In turn, it is possible that COVID-19 vaccine boosted cross-reactive immune responses may influence vaccine-induced protection 7 . Indeed, it will be important to explore whether COVID-19 vaccination can boost any infection-induced cross-reactive T cell memory, and whether this affects robustness of protection from SARS-CoV-2 variants or wider coronaviruses.…”

“…Several studies 5,6 have illustrated that the correlates of immunity to SARS-CoV-2 are implicated by the presence of pre-existing immunological memory conferred from crossreactivity to other viruses. On the one hand such cross-reactivity could modulate disease severity, vaccine response and/or protection against SARS-CoV-2 and its variants via presence of antigen-specific memory T cells 7 . Conversely, cross-reactivity may provoke immunopathology through mechanisms such as antibody-dependent enhancement of infection, with the potential for virus-induced autoimmune disease in years to come 8 .…”

Hybrid immunity

“…Antibodies are clearly involved in protection against SARS-CoV-2 reinfection, but evidence also points to contributions from T cells (1). T cell responses against SARS-CoV-2 in natural infection are quite broad (1), and most T cell epitopes are not mutated in VOCs, indicating that the contributions of T cells to protective immunity are likely to be retained (4,15). Most of the COVID-19 vaccines in use consist of a single antigen, spike, whereas 25 different viral proteins are present in SARS-CoV-2.…”

Structural basis for recognition of two HLA-A2-restricted SARS-CoV-2 spike epitopes by public and private T cell receptors

“…Based on these and related findings, intensive efforts are underway to identify SARS-CoV-2 epitopes that elicit protective T cell responses against this virus and to delineate TCR repertoires specific for these epitopes (6,10,13,17,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). T cell responses to ORFs encoding both structural (S, M, N) and nonstructural (nsp3, 4, 6, 7, 12, 13) proteins have been detected, with the S (spike) and N (nucleocapsid) proteins inducing the most robust CD8 + T cell responses in most studies.…”