Abstract
T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.
Highlights
Dominant T cell epitopes Subdominant T cell epitopesBorders: SARS-CoV-2-specific T cell epitopes Cross-reactive T cell epitopesSARS-CoV-2-derived HLA class I (a) and HLA-DR (b) T cell epitopes
Summary of immunogenic SARS-CoV-2-derived HLA class I T cell epitopes as defined by IFN-γ enzyme-linked immunospot (ELISPOT) assays with detected recognition frequencies in the SARS and PRE groups
To allow for the detection of even very small SARS-CoV-2 epitope-recognizing T cell populations especially in unexposed donors, where SARS-CoV-2 cross-reactive T cells were below the detection limit in ex vivo analyses, epitope definition was based on a 12-d pre-stimulation protocol before a routine 18–24-h ELISPOT assay
Summary
Dominant T cell epitopes Subdominant T cell epitopesBorders: SARS-CoV-2-specific T cell epitopes Cross-reactive T cell epitopesSARS-CoV-2-derived HLA class I (a) and HLA-DR (b) T cell epitopes. SARS-CoV2-specific T cell epitopes with responses detected exclusively in the SARS group are marked with a red frame, cross-reactive epitopes with immune responses detected in the PRE group are marked with a blue frame. In line with the findings obtained with the screening group (SARS group 1), the intensity (in terms of spot counts per 5 × 105 cells) of HLA class I T cell responses was significantly lower compared to HLA-DR T cell responses, both for specific (median calculated spot count HLA class I 379, HLA-DR 760) and cross-reactive ECs (median calculated spot count HLA class I 86, HLA-DR 846; Fig. 5f,g). In line with the differences in recognition rates observed between SARS group 1 and PRE group A, the intensity of T cell responses to cross-reactive ECs was significantly lower in the PRE group (median calculated spot count HLA class I 14, HLA-DR 346) compared to the SARS group (Fig. 5g)
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