SARS-CoV-2 Epitopes Are Recognized by a Public and Diverse Repertoire of Human T Cell Receptors

Abstract

Understanding the hallmarks of the immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed antibody and T cell reactivity in convalescent COVID-19 patients and healthy donors sampled both prior to and during the pandemic. Healthy donors examined during the pandemic exhibited increased numbers of SARS-CoV-2-specific T cells, but no humoral response. Their probable exposure to the virus resulted in either asymptomatic infection without antibody secretion, or activation of pre-existing immunity. In convalescent patients, we observed a public and diverse T cell response to SARS-CoV-2 epitopes, revealing T cell receptor (TCR) motifs with germline-encoded features. Bulk CD4 + and CD 8+ T cell responses to the spike glycoprotein were mediated by groups of homologous TCRs, some of them shared across multiple donors. Overall, our results demonstrate that the T cell response to SARS-CoV-2, including the identified set of TCRs, can serve as a useful biomarker for surveying antiviral immunity.

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

“…( Schultheiß et al., 2020 ), Shomuradova et al. ( Shomuradova et al., 2020 ) and Alsoussi et al. ( Alsoussi et al., 2020 ).…”

In silico T cell epitope identification for SARS-CoV-2: Progress and perspectives

“…This data has started to emerge from immunological assays that analyze immune responses in COVID-19 patients. As of 8 September 2020, we found eight experimental studies [ 8 , 9 , 115 , [176] , [177] , [178] , [179] , [180] ], reviewed in [ 181 ], as well as an additional study [ 182 ], that reported positive T cell immune responses from blood samples of convalescent COVID-19 patients against epitopes derived from SARS-CoV-2 proteins. Compiling data from these nine studies yielded a total of 324 (unique) epitopes.…”

“…Of these, some studies obtained a set of peptides to synthesize using one or more of the in silico epitope prediction methods, which were then used to stimulate the PBMCs. Three such studies [ 8 , 9 , 180 ] used NetMHCpan-4.0, two studies [ 177 , 182 ] used NetMHC4.0, while one study [ 115 ] used HLAThena and NeonMHC2 to select the set of peptides to synthesize. Two of these studies [ 8 , 182 ] also investigated a few epitopes that were predicted in [ 20 , 22 ] using SARS-CoV immunological data.…”

“…

Fig. 5 Results obtained for the 324 experimentally-determined SARS-CoV-2 T cell epitopes [ 8 , 9 , 115 , [176] , [177] , [178] , [179] , [180] , 182 ] when they were provided as input to the computational tools most commonly used in the reviewed SARS-CoV-2 in silico studies for refinement of epitopes obtained by peptide-HLA binding prediction methods. Positive outcomes indicate the number of epitopes the computational tool predicts to have the characteristic (immunogenicity, IFN-γ production, allergenicity, toxicity) being tested, and vice versa for negative outcomes.

…”

Single-cell RNA sequencing revealsin vivosignatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’

“…Immunodominant SARS-CoV-2 antigen specificities have been identified with unprecedented speed for an emerging pathogen, and phenotypic characterization of antigen-reactive T cells has quickly been performed by a plethora of studies 6,7,16,[8][9][10][11][12][13][14][15] . While there is general agreement that SARS-CoV-2-reactive T cells are activated and differentiate during the course of the immune response, the extents of activation and differentiation are controversial 4,5 .…”