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Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients.
Lu, Xiuyuan; Hosono, Yuki; Nagae, Masamichi; Ishizuka, Shigenari; Ishikawa, Eri; Motooka, Daisuke; Ozaki, Yuki; Sax, Nicolas; Maeda, Yuichi; Kato, Yasuhiro; Morita, Takayoshi; Shinnakasu, Ryo; Inoue, Takeshi; Onodera, Taishi; Matsumura, Takayuki; Shinkai, Masaharu; Sato, Takashi; Nakamura, Shota; Mori, Shunsuke; Kanda, Teru; Nakayama, Emi E; Shioda, Tatsuo; Kurosaki, Tomohiro; Takeda, Kiyoshi; Kumanogoh, Atsushi; Arase, Hisashi; Nakagami, Hironori; Yamashita, Kazuo; Takahashi, Yoshimasa; Yamasaki, Sho.
  • Lu X; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Hosono Y; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Nagae M; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Ishizuka S; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Ishikawa E; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Motooka D; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Ozaki Y; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Sax N; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Maeda Y; Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Kato Y; Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Morita T; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Shinnakasu R; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Inoue T; KOTAI Biotechnologies, Inc., Suita, Japan.
  • Onodera T; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Matsumura T; Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Shinkai M; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Sato T; Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Nakamura S; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Mori S; Department of Immunopathology, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Kanda T; Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Nakayama EE; Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Shioda T; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.
  • Kurosaki T; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan.
  • Takeda K; Tokyo Shinagawa Hospital, Tokyo, Japan.
  • Kumanogoh A; Tokyo Shinagawa Hospital, Tokyo, Japan.
  • Arase H; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Nakagami H; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Yamashita K; Laboratory of Immunochemistry, Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Takahashi Y; Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
  • Yamasaki S; Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
J Exp Med ; 218(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1467277
ABSTRACT
Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Helper-Inducer / Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Adult / Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Jem.20211327

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Full text: Available Collection: International databases Database: MEDLINE Main subject: T-Lymphocytes, Helper-Inducer / Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Adult / Female / Humans / Male Language: English Year: 2021 Document Type: Article Affiliation country: Jem.20211327