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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    Allelic variation in Class I HLA determines pre-existing memory responses to SARS-CoV-2 that shape the CD8 HGNC+ T cell repertoire upon viral exposure

    Authors: Joshua M Francis; Del Leistritz-Edwards; Augustine Dunn; Christina Tarr; Jesse Lehman; Conor Dempsey; Andrew Hamel; Violeta Rayon; Gang Liu; Yuntong Wang; Marcos Wille; Melissa Durkin; Kane Hadley; Aswathy Sheen; Benjamin Roscoe; Mark Ng; Graham Rockwell; Margaret Manto; Elizabeth Gienger; Joshua Nickerson; - MGH COVID-19 Collection and Processing Team; Amir Moarefi; Michael Noble; Thomas Malia; Philip D Bardwell; William Gordon; Joanna Swain; Mojca Skoberne; Karsten Sauer; Tim Harris; Ananda W Goldrath; Alex K Shalek; Anthony J Coyle; Christophe Benoist; Daniel C Pregibon

    doi:10.1101/2021.04.29.441258 Date: 2021-04-29 Source: bioRxiv

    Effective presentation of antigens by HLA class I molecules to CD8 HGNC+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multi-omic technology to generate the first unified ex vivo characterization of the CD8 HGNC+ T cell response to SARS-CoV-2 across 4 major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCR HGNC a/b sequence diversity, and the utilization of pre-existing SARS-CoV-2 reactive memory T MESHD cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations influence pre-existing immunity to SARS-CoV-2 and shape the immune repertoire upon subsequent viral exposure.

    Identification, crystallization and epitope determination of public TCR HGNC shared and expanded in COVID-19 MESHD patients

    Authors: Xiuyuan Lu; Yuki Hosono; Shigenari Ishizuka; Masamichi Nagae; Eri Ishikawa; Daisuke Motooka; Yuki Ozaki; Nicolas Sax; Ryo Shinnakasu; Takeshi Inoue; Taishi Onodera; Takayuki Matsumura; Masaharu Shinkai; Takashi Sato; Shota Nakamura; Shunsuke Mori; Teru Kanda; Emi E. Nakayama; Tatsuo Shioda; Tomohiro Kurosaki; Hisashi Arase; Kazuo Yamashita; Yoshimasa Takahashi; Sho Yamasaki

    doi:10.1101/2021.03.23.436573 Date: 2021-03-23 Source: bioRxiv

    T cells play pivotal roles in protective immunity against SARS-CoV-2 infection MESHD. Follicular helper T (Tfh) cells mediate the production of antigen-specific antibodies; however, T cell receptor ( TCR HGNC) clonotypes used by SARS-CoV-2-specific Tfh cells have not been well characterized. Here, we first identified and crystallized public TCR HGNC of Tfh clonotypes that are shared and expanded in unhospitalized COVID-19 MESHD-recovered patients. These clonotypes preferentially recognized SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN epitopes which are conserved among emerging SARS-CoV-2 variants. These clonotypes did not react with S proteins PROTEIN derived from common cold human coronaviruses, but cross-reacted with symbiotic bacteria, which might confer the publicity. Among SARS-CoV-2 S epitopes MESHD, S864-882, presented by frequent HLA-DR alleles, could activate multiple public Tfh clonotypes in COVID-19 MESHD-recovered patients. Furthermore, S864-882-loaded HLA tetramer preferentially bound to CD4+ T cells expressing CXCR5 HGNC. In this study, we identified and crystallized public TCR HGNC for SARS-CoV-2 that may contribute to the prevention of COVID-19 MESHD aggravation.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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