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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ORF1 (3)

ProteinN (3)

ORF3a (1)

ProteinM (1)

ProteinS (1)


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SARS-CoV-2 Proteins
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    SARS-CoV-2 genome-wide mapping of CD8 HGNC T cell recognition reveals strong immunodominance and substantial CD8 HGNC T cell activation in COVID-19 MESHD patients

    Authors: Sunil Kumar Saini; Ditte Stampe Hersby; Tripti Tamhane; Helle Rus Povlsen; Susana Patricia Amaya Hernandez; Morten Nielsen; Anne Ortved Gang; Sine Reker Hadrup; Sergio Poli; Lance M. Peter; Chase J. Taylor; Jessica B. Blackburn; Bradley W. Richmond; Andrew G. Nicholson; Doris Rassl; William A. Wallace; Ivan O. Rosas; R. Gisli Jenkins; Naftali Kaminski; Jonathan A. Kropski; Nicholas E. Banovich; - Human Cell Atlas Lung Biological Network; Renata J Medeiros; Juliana MM Gomes; Mara Souza Junqueira; Katia Conceicao; Leticia G. Pontes; Antonio Condino Neto; Andrea C Perez; Leonardo G Barcellos; Jose Dias Correa Junior; Erick Gustavo Dorlass; Niels OS Camara; Edison Luiz Durigon; Fernando Q Cunha; Rafael H Nobrega; Glaucia M Machado-Santelli; Chuck S Farah; Flavio P Veras; Jorge Galindo-Villegas; Leticia Costa-Lotufo; Thiago M Cunha; Roger Chammas; Luciani R. Carvalho; Cristiane R. Guzzo; Ives Charlie-Silva

    doi:10.1101/2020.10.19.344911 Date: 2020-10-19 Source: bioRxiv

    To understand the CD8 HGNC+ T cell immunity related to viral protection and disease severity in COVID-19 MESHD, we evaluated the complete SARS-CoV-2 genome (3141 MHC-I binding peptides) to identify immunogenic T cell epitopes, and determine the level of CD8 HGNC+ T cell involvement using DNA-barcoded peptide-major histocompatibility complex (pMHC) multimers. COVID-19 MESHD patients showed strong T cell responses, with up to 25% of all CD8 HGNC+ lymphocytes specific to SARS-CoV-2-derived immunodominant epitopes, derived from ORF1 PROTEIN ( open reading frame 1 PROTEIN), ORF3 HGNC, and Nucleocapsid (N) protein PROTEIN. A strong signature of T cell activation was observed in COVID-19 MESHD patients, while no T cell activation was seen in the non-exposed and high exposure risk healthy donors. Interestingly, patients with severe disease displayed the largest T cell populations with a strong activation profile. These results will have important implications for understanding the T cell immunity to SARS-CoV-2 infection MESHD, and how T cell immunity might influence disease development.

    Broad and strong memory CD4 HGNC+ and CD8 HGNC+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 MESHD patients.

    Authors: Tao Dong; Yanchun Peng; Alexander J Mentzer; Guihai Liu; Xuan Yao; Zixi Yin; Danning Dong; Wanwisa Dejnirattisai; Lance Turtle; Timothy Rostron; Krishanthi Subramaniam; Paul Thomson; Ping Zhang; Christina Dold; Jeremy Ratcliff; Thushan de Silva; Paul Sopp; Dannielle Wellington; Ushani Rajapaksa; Wayne Paes; Persephone Borrow; Benedikt M Kessler; Jeremy W Fry; Nikolai F Schwabe; Malcolm G Semple; J Kenneth Baillie; Peter JM Openshaw; Richard J Cornall; Chris Conlon; Gavin Screaton; Paul Klenerman; Juthathip Mongkolsapaya; Andrew McMichael; Julian C Knight; Graham Ogg; Peter Simmonds; Teresa Lockett; Robert Levin; Shona C Moore; Mariolina Salio; Giorgio Napolitani; Yi-Ling Chen; Susie Dunachie; Piyada Supasa; Chang Liu; Cesar Lopez-Camacho; Jose Slon-Campos; Yuguang Zhao; David I Stuart; Guido Paeson; Jonathan Grimes; Fred Antson; Oliver W Bayfield; Dorothy EDP Hawkins; De-Sheng Ker; Azim Ansari; Ellie Barnes; John Frater; Georgina Kerr; Philip Goulder

    doi:10.1101/2020.06.05.134551 Date: 2020-06-08 Source: bioRxiv

    COVID-19 MESHD is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19 MESHD, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFN{gamma} based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1 PROTEIN. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 MESHD were significantly higher in severe compared to mild COVID-19 MESHD cases, and this effect was most marked in response to spike, membrane, and ORF3a PROTEIN proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti- Nucleoprotein PROTEIN (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4 HGNC+ and/or CD8 HGNC+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M PROTEIN, 32%, 47%) and one in the nucleoprotein PROTEIN (Np, 35%). CD8 HGNC+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory MESHD phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8 HGNC+ T cells than spike-specific CD8 HGNC+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8 HGNC+ to CD4 HGNC+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections MESHD. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non- spike proteins PROTEIN within future COVID-19 MESHD vaccine design.

    Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals

    Authors: Nina Le Bert; Anthony Tanoto Tan; Kamini Kunasegaran; Christine Y. L. Tham; Morteza Hafezi; Adeline Chia; Melissa Chng; Meiyin Lin; Nicole Tan; Martin Linster; Wan Ni Chia; Mark I-Cheng Chen; Lin-Fa Wang; Eng Eong Ooi; Shirin Kalimuddin; Paul Anantharajal Tambyah; Jenny Guek-Hong Low; Yee-Joo Tan; Antonio Bertoletti

    doi:10.1101/2020.05.26.115832 Date: 2020-05-27 Source: bioRxiv

    Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural ( nucleocapsid protein PROTEIN, NP) and non-structural (NSP-7 and NSP13 PROTEIN of ORF1 PROTEIN) regions of SARS-CoV-2 in convalescent from COVID-19 MESHD (n=24). In all of them we demonstrated the presence of CD4 HGNC and CD8 HGNC T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 MESHD or contact with SARS/ COVID-19 MESHD patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 PROTEIN and 13, which were rarely detected in COVID-19 MESHD- and SARS-recovered patients. Epitope characterization of NSP7 PROTEIN-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection MESHD is of paramount importance for the management of the current COVID-19 pandemic MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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