CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entire SARS-CoV-2 proteome and show kinetics of early differentiation

Abstract

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

SARS CoV-2 infections in healthcare workers with a pre-existing T-cell response: a prospective cohort study

“…Second, initial T-cell evaluation was performed 5e6 months before infection, and we cannot preclude a slight decrease in T-cell immunity during this period. Finally, we did not include T-cell response to other structural proteins, such as ORF1a, which have been showed to be immunodominant in some studies [13].…”

Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens

“…Antigen-specific T-cell responses evaluated by exposing peripheral blood mononuclear cells (PBMC) to peptide pools ( 7-10 ) suggest that Spike (the target of most COVID-19 vaccines), nucleocapsid and M envelope proteins are the most relevant CD4+ and CD8+ T cell targets ( 7, 8, 10-12 ). On the other hand, peptide-MHC tetramer staining, used to screen epitopes for T cell recognition across different HLA alleles, found that CD8+ T cells specific to nucleocapsid were present at a higher frequency than those specific for Spike-or non-structural proteins ( 13, 14 ). In several studies, the magnitude of SARS-CoV-2-specific IgG and IgA titers correlated with the SARS-CoV-2 T cell response ( 10, 11, 15 ).…”

Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice

“…However, only several reports are thus far available about the vaccine candidate T cell epitopes that have been validated by functional experiments. 408 CD8 + T cell epitopes on-silicon predicted were applied in multiplexed peptide-MHC tetramer staining to detect the PBMCs from 30 convalescent COVID-19 patients, then 132 positive reactions were obtained with the validation of 42 CD8 + T cell epitopes presented by 6 HLA molecules (HLA-A0101, A0201, A0301, A1101, A2402 and B0702) 32 . Prackar et al tested the binding stability of 777 CD4 + and CD8 + T cell epitopes that were predicted to be good binders across 11 MHC allotypes using an in vitro peptide MHC stability assay, and found that 174 peptides can stably bind to the HLA allotypes (HLA-A0101, A0201, A0301, A1101, A2402, B4001, C0102, C0401, C0701, C0702, DRB10401), of which 126 have not been reported previously 31 .…”

“…However, most studies have utilized pools of predicted or overlapping peptides spanning the sequences of different SARS-CoV-2 proteins 22,23,24,25,26,27,28 . The functionally validated T cell epitopes are still limited and have thus far come from only a few laboratories 10,11,29,30,31,32 . These T cell epitopes are presented only by several HLA class I or II molecules and the precise HLA restrictions of each epitope will need to be further defined.…”