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

Shomuradova, Alina S.; Vagida, Murad; Sheetikov, Savely; Zornikova, Ksenia V.; Kiryukhin, Dmitry; Titov, Aleksei; Peshkova, Iuliia O.; Khmelevskaya, Alexandra; Dianov, Dmitry Vladimirovich; Malasheva, Maria; Shmelev, Anton; Serdyuk, Yana; Bagaev, Dmitry; Pivnyuk, Anastasia; Shcherbinin, Dmitrii S.; Maleeva, Alexandra V.; Shakirova, Naina T.; Pilunov, Artem; Malko, Dmitry B.; Хамаганова, Е Г; Biderman, Bella; Ivanov, Alexander; Shugay, Mikhail

doi:10.2139/ssrn.3640836

Cited by 12 publications

(6 citation statements)

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“…A search for TCRbeta amino acid sequences of responding clones in VDJdb [ the EBV (Epstein-Barr virus) epitope presented by the HLA-A*03 MHC allele, which is absent in both donors (SI Table 1). On day 25 post-infection donor M participated in study by Shomuradova et al [24] (as donor p1434), where his CD8+ T cells were stained with HLA-A*02:01-YLQPRTFLL MHC-I tetramer. TCRalpha and TCRbeta of FACS-sorted tetramer-positive cells were sequenced and deposited to VDJdb (see [24] for the experimental details).…”

Section: Resultsmentioning

confidence: 99%

“…On day 25 post-infection donor M participated in study by Shomuradova et al [24] (as donor p1434), where his CD8+ T cells were stained with HLA-A*02:01-YLQPRTFLL MHC-I tetramer. TCRalpha and TCRbeta of FACS-sorted tetramer-positive cells were sequenced and deposited to VDJdb (see [24] for the experimental details). We matched these tetramer-specific TCR sequences to our longitudinal dataset (see Fig.…”

Section: Resultsmentioning

confidence: 99%

“…a, SARS-CoV-2-specific TCRs are independently identified by clonal contraction. Each dot correspond to the frequency of HLA-A*02:01-YLQPRTFLL-tetramer specific TCRbeta clonotypes in bulk repertoire of donor M (donor p1434 from[24]) at each timepoint. Green dots correspond to clonotypes independently identified as contracting in our longitudinal dataset.…”

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confidence: 99%

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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

Minervina

Komech

Titov

et al. 2020

Preprint

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COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

Minervina

Komech

Titov

et al. 2020

Preprint

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“…Results compiled from 8 experimental studies of T cell responses in a total of 1,259 convalescent COVID-19 patients (Le Bert et al, 2020;Chour et al, 2020;Peng et al, 2020;Nelde et al, 2020;Poran et al, 2020;Shomuradova et al, 2020;Ferretti et al, 2020;Snyder et al, 2020) revealed 303 unique T cell epitopes. Of these, 71 are CD8 + (HLA class I restricted), 21 are CD4 + (HLA class II restricted), while 211 epitopes had no HLA allele information reported ( Figure 1A).…”

Section: Sars-cov-2 T Cell Epitopes Identified By Studies Of Convalesmentioning

confidence: 99%

“…Data was compiled from 8 immunological studies (as of 7 August 2020) reporting SARS-CoV-2 T cell epitopes in convalescent COVID-19 patients. More specifically, epitope data was extracted from Figure 3 in (Chour et al, 2020), Table 1 in (Shomuradova et al, 2020), Extended Data Tables 2 and 3 in (Nelde et al, 2020), Figure 3 in (Poran et al, 2020), Table 1 in (Ferretti et al, 2020), Table 1 in (Le Bert et al, 2020), Tables 1 and 2 in (Peng et al, 2020), and data deposited by authors of (Snyder et al, 2020) in the Immune Epitope Database (IEDB).…”

Section: T Cell Epitope Data Derived From Convalescent Covid-19 Patientsmentioning

confidence: 99%

Epitopes targeted by T cells in convalescent COVID-19 patients

Quadeer

Ahmed

McKay

2020

Preprint

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There is growing evidence pointing to the protective role of T cells against COVID-19. Vaccines eliciting targeted T cell responses have the potential to provide robust, long-lasting immunity. However, their design requires knowledge of the SARS-CoV-2-specific epitopes that can elicit a T cell response and confer protection across a wide population. Here, we provide a unified description of emerging data of SARS-CoV-2 T cell epitopes compiled from results of 8 independent studies of convalescent COVID-19 patients. We describe features of these epitopes relevant for vaccine design, while indicating knowledge gaps that can, in part, be augmented using prior immunological data from SARS-CoV. The landscape of SARS-CoV-2 T cell epitopes that we describe can help guide SARS-CoV-2 vaccine development as well as future immunological studies. A web-based platform has also been developed to complement these efforts.

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Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics

Sivapalan¹,

Liu

Chakraborty³

et al. 2021

Sci Rep

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The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics.

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

Cited by 12 publications

References 0 publications

Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection

Epitopes targeted by T cells in convalescent COVID-19 patients

Virus Induced Lymphocytes (VIL) as a novel viral antigen-specific T cell therapy for COVID-19 and potential future pandemics

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