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 1,400 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 immune escape by SARS-CoV-2 variants.

Keywords: CD4; CD8; SARS-CoV-2; T cells; epitopes.

Figure 1

Distribution of CD4 and CD8 epitopes by SARS-CoV-2 antigen The fraction of known CD4 and CD8 epitopes derived from recognized SARS-CoV-2 antigens is shown in (A) and (B), respectively. The number of epitopes derived from each antigen as a function of antigen size is plotted in (C) and (D) for CD4⁺ (light blue) and CD8⁺(red) T cells, respectively; p values were calculated using a simple linear regression. (E) and (F) show the number of studies that probed responses to each antigen. All the source data used in these analyses were derived from the papers cited within Tables 1 and S1.

Figure 2

Identification of immunodominant antigenic regions The IEDB’s Immunome Browser tool was utilized to identify potential antigenic regions across the entire SARS-CoV-2 proteome. After searching for SARS-CoV-2-derived CD4⁺ (light blue) and CD8⁺(red) T cell epitopes, individual antigens were selected for further evaluation. From the antigen-specific Immunome Browser link, data was downloaded as an Excel file to obtain position-specific lower bound response frequency scores (RF), defined as the number of individuals and assays reporting positive responses to a peptide including that particular residue. For visualization, RF scores for each residue were recalculated to represent a sliding 10-residue window. Position-specific RF values for CD4 (light blue) and CD8 (red) epitopes are shown for the most dominant viral antigens: spike (A and B); M and N (C and D); nsp3 and nsp12 (E and F). The receptor binding domain region of the spike protein, is indicated in yellow in A and B because it is critically recognized by neutralizing antibodies and implicated in viral cell entry.

Figure 3

Defined HLA class I and class II restrictions HLA-restricted epitopes have been identified for 30 class I (red, A) and 45 class II (light blue, B) molecules. The charts shows the number of restricted epitopes associated with each allele (alleles shown on the horizontal axis).