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

Lu, Xiuyuan; Hosono, Yuki; Ishizuka, Shigenari; Nagae, Masamichi; Ishikawa, Eri; Motooka, Daisuke; Ozaki, Yuki; Sax, Nicolas; 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; Arase, Hisashi; Yamashita, Kazuo; Takahashi, Yoshimasa; Yamasaki, Sho

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