1. Identification of conserved SARS-CoV-2 spike epitopes that expand public cTfh clonotypes in mild COVID-19 patients
- Author
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Tomohiro Kurosaki, Nicolas Sax, Takashi Sato, Takayuki Matsumura, Yuki Hosono, Eri Ishikawa, Shota Nakamura, Taishi Onodera, Emi E. Nakayama, Daisuke Motooka, Yuki Ozaki, Masamichi Nagae, Hisashi Arase, Kiyoshi Takeda, Xiuyuan Lu, Masaharu Shinkai, Tatsuo Shioda, Yoshimasa Takahashi, Yasuhiro Kato, Shigenari Ishizuka, Kazuo Yamashita, Takeshi Inoue, Atsushi Kumanogoh, Hironori Nakagami, Yuichi Maeda, Sho Yamasaki, Teru Kanda, Shunsuke Mori, Takayoshi Morita, and Ryo Shinnakasu
- Subjects
Adult ,Male ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,T cell ,Immunology ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Biology ,Antibodies, Viral ,Lymphocyte Activation ,Epitope ,Article ,Infectious Disease and Host Defense ,Antigen ,HLA Antigens ,medicine ,Immunology and Allergy ,Humans ,In patient ,SARS-CoV-2 ,COVID-19 ,T-Lymphocytes, Helper-Inducer ,Acquired immune system ,medicine.anatomical_structure ,Spike Glycoprotein, Coronavirus ,Female - Abstract
Through single-cell TCR and RNA sequencing, the authors identified public cTfh clonotypes expanded in recovered COVID-19 patients and determined their epitopes in the specific regions of spike protein conserved among emerging SARS-CoV-2 variants, which are candidates for booster antigens., 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.
- Published
- 2021