Xiuyuan Lu: Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Yuki Hosono: Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Masamichi Nagae: Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Shigenari Ishizuka: Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Eri Ishikawa: Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Daisuke Motooka: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Yuki Ozaki: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Nicolas Sax: KOTAI Biotechnologies, Inc., Suita, Japan. ORCID
Yuichi Maeda: Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
Yasuhiro Kato: Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
Takayoshi Morita: Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
Ryo Shinnakasu: Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Takeshi Inoue: Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Taishi Onodera: Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan. ORCID
Takayuki Matsumura: Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo, Japan. ORCID
Masaharu Shinkai: Tokyo Shinagawa Hospital, Tokyo, Japan. ORCID
Takashi Sato: Tokyo Shinagawa Hospital, Tokyo, Japan. ORCID
Shota Nakamura: Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Shunsuke Mori: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Teru Kanda: Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan. ORCID
Emi E Nakayama: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Tatsuo Shioda: Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Tomohiro Kurosaki: Laboratory of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, Suita, Japan. ORCID
Kiyoshi Takeda: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
Atsushi Kumanogoh: Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
Hisashi Arase: Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. ORCID
Hironori Nakagami: Department of Health Development and Medicine, Graduate School of Medicine, Osaka University, Suita, Japan. ORCID
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.
