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

Lu, X.; Hosono, Y.; Ishizuka, S.; Nagae, M.; Ishikawa, E.; Motooka, D.; Ozaki, Y.; Sax, N.; Shinnakasu, R.; Inoue, T.; Onodera, T.; Matsumura, T.; Shinkai, M.; Sato, T.; Nakamura, S.; Mori, S.; Kanda, T.; Nakayama, E. E.; Shioda, T.; Kurosaki, T.; Arase, H.; Yamashita, K.; Takahashi, Y.; Yamasaki, S.

doi:10.1101/2021.03.23.436573

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bioRxiv · 10.1101/2021.03.23.436573

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

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Abstract

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.

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Lu, X., Hosono, Y., Ishizuka, S., Nagae, M., Ishikawa, E., Motooka, D., Ozaki, Y., Sax, N., Shinnakasu, R., Inoue, T., Onodera, T., Matsumura, T., Shinkai, M., Sato, T., Nakamura, S., Mori, S., Kanda, T., Nakayama, E. E., Shioda, T., Kurosaki, T., Arase, H., Yamashita, K., Takahashi, Y., Yamasaki, S.. 2021-03-23. Identification, crystallization and epitope determination of public TCR shared and expanded in COVID-19 patients. https://doi.org/10.1101/2021.03.23.436573

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