scholarly journals SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors

Author(s):  
Alina S. Shomuradova ◽  
Murad S. Vagida ◽  
Savely A. Sheetikov ◽  
Ksenia V. Zornikova ◽  
Dmitry Kiryukhin ◽  
...  

SummaryUnderstanding the hallmarks of the adaptive immune response to SARS-CoV-2 is critical for fighting the COVID-19 pandemic. We assessed the antibody and T-cell reactivity in COVID-19 convalescent patients and healthy donors sampled both prior to and during the pandemic. The numbers of SARS-CoV-2-specific T cells were increased in healthy donors examined during COVID-19. Combined with the absence of symptoms and humoral response across that group, this finding suggests that some individuals might be protected by T-cell cross-reactivity. In convalescent patients we observed public and diverse T-cell response to SARS-CoV-2 epitopes, revealing T-cell receptor motifs with germline-encoded features. Bulk CD4+ and CD8+ T-cell responses to Spike glycoprotein were mediated by groups of homologous T-cell receptors, some of them shared across multiple donors. Overall, our results demonstrate that T-cell response to SARS-CoV-2, including the identified set of specific T-cell receptors, can serve as a useful biomarker for surveying viral exposure and immunity.

Hepatology ◽  
2006 ◽  
Vol 43 (3) ◽  
pp. 602-611 ◽  
Author(s):  
Patrick T.F. Kennedy ◽  
Simonetta Urbani ◽  
Rebecca A. Moses ◽  
Barbara Amadei ◽  
Paola Fisicaro ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5475-5475
Author(s):  
David M. Kofler ◽  
Markus Chmielewski ◽  
Heike Koehler ◽  
Tobias Riet ◽  
Patrick Schmidt ◽  
...  

Abstract Recombinant T cell receptors with defined specificity against tumor cells are a promising experimental approach in the elimination of residual leukemia and lymphoma cells. It is so far unresolved whether regulatory T cells with suppressor activities impair the efficiency of cytolytic T cells grafted with a recombinant immunoreceptor. The frequency of regulatory T cells is highly increased in tumor patients and their suppressive function seems to play a role in the fail of an autologous T cell response against the malignant cells. In this study we analyzed the antigen-triggered, specific activation of receptor grafted T cells in the presence or absence of regulatory CD4+CD25high T cells. CD3+ T cells were grafted with CEA-specific immunoreceptors containing the CD3-zeta signaling domain for T cell activation. Co-cultivation of receptor grafted effector T cells together with regulatory T cells repressed proliferation of the effector cells and decreased IL-2 secretion. Secretion of IFN-gamma and IL-10 was not impaired. Interestingly, the cytotoxicity of grafted effector T cells towards CEA-expressing tumor cells was not impaired by regulatory T cells in vitro. To evaluate the relevance in vivo, we used a Crl:CD1 Nu/Nu mouse model to assess growth of CEA+ tumor cells in the presence of receptor grafted effector T cells and of regulatory T cells. Mice inoculated with tumor cells together with CD3+ effector T cells without immunoreceptor and regulatory T cells developed earlier tumors with faster growth kinetics compared to mice that were inoculated with tumor cells, CD3+ T cells and CD4+CD25- control T cells. Using effector T cells that were equipped with a recombinant CEA-specific CD3-zeta immunoreceptor, 2 of 5 mice developed a tumor in the presence of regulatory T cells while none of the mice developed a tumor in the absence of regulatory T cells. Taken together, regulatory T cells obviously impair an antigen-specific, anti-tumor T cell attack in vivo. This seems to be due to repression of proliferation of the effector T cells and not to diminished cytotoxicity. These findings have major impact on the design of clinical studies involving adoptively transferred effector T cells.


2016 ◽  
Vol 213 (7) ◽  
pp. 1331-1352 ◽  
Author(s):  
Lance Turtle ◽  
Tanushka Bali ◽  
Gemma Buxton ◽  
Savita Chib ◽  
Sajesh Chan ◽  
...  

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8+ and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4+ and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4+ T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4+ and CD8+ T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.


Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 30
Author(s):  
Perrine Pégorier ◽  
Morgane Bertignac ◽  
Viviane Nguefack Ngoune ◽  
Géraldine Folch ◽  
Joumana Jabado-Michaloud ◽  
...  

The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response expressed by T cells, which specifically recognize processed antigens, presented as peptides by the highly polymorphic major histocompatibility (MH) proteins. T cell receptors (TR) are divided into two groups, αβ and γδ, which express distinct TR containing either α and β, or γ and δ chains, respectively. The TRα locus (TRA) and TRδ locus (TRD) of bovine (Bos taurus) and the sheep (Ovis aries) have recently been described and annotated by IMGT® biocurators. The aim of the present study is to present the results of the biocuration and to compare the genes of the TRA/TRD loci among these ruminant species based on the Homo sapiens repertoire. The comparative analysis shows similarities but also differences, including the fact that these two species have a TRA/TRD locus about three times larger than that of humans and therefore have many more genes which may demonstrate duplications and/or deletions during evolution.


2000 ◽  
Vol 51 (2) ◽  
pp. 176-185 ◽  
Author(s):  
Jose ◽  
Wolk ◽  
Lorenzen ◽  
Wenschuh ◽  
Meyer

2020 ◽  
Vol 18 ◽  
pp. 443-456
Author(s):  
Rory M. Crean ◽  
Bruce J. MacLachlan ◽  
Florian Madura ◽  
Thomas Whalley ◽  
Pierre J. Rizkallah ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Chloe H. Lee ◽  
Mariolina Salio ◽  
Giorgio Napolitani ◽  
Graham Ogg ◽  
Alison Simmons ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document