Functional characterization of CD4+ T-cell receptors cross-reactive for SARS-CoV-2 and endemic coronaviruses
| Autor: | Drew M. Pardoll, Bezawit A. Woldemeskel, Franco R. D'Alessio, Hongkai Ji, Emily Han-Chung Hsiue, Kellie N. Smith, Justina X. Caushi, Jiajia Zhang, Shibin Zhou, Jonathan D. Powell, Alvaro A. Ordonez, Rufiaat Rashid, Arbor G. Dykema, Elizabeth A. Thompson, Joel N. Blankson, Boyang Zhang, Caroline C. Garliss, Dilshad Choudhury, Sadhana Bom, Sampriti Thapa, Laurene S. Cheung, Dipika Singh, Andrea L. Cox, Andrew Pekosz, Abena K. Kwaa, Katherine Cascino, Srinivasan Yegnasubramanian, Luis Aparicio |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine viruses medicine.medical_treatment T cell Receptors Antigen T-Cell Epitopes T-Lymphocyte chemical and pharmacologic phenomena Context (language use) Cross Reactions Biology Jurkat cells Jurkat Cells 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Antigen medicine Humans Avidity Receptor Aged SARS-CoV-2 T-cell receptor COVID-19 General Medicine Middle Aged 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Female Clinical Medicine Immunologic Memory |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| DOI: | 10.1172/jci146922 |
| Popis: | BACKGROUND: Recent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2. METHODS: We used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2–unexposed donors. Confirmation of SARS-CoV-2/CCC crossreactivity and assessments of functional avidity were performed using a TCR cloning and transfection system. RESULTS: Memory CD4(+) T cell clonotypes that crossrecognized the S proteins of SARS-CoV-2 and at least one other CCC were detected in 65% of CCPs and unexposed donors. Several of these TCRs were shared among multiple donors. Crossreactive T cells demonstrated significantly impaired SARS-CoV-2–specific proliferation in vitro relative to monospecific CD4(+) T cells, which was consistent with lower functional avidity of their TCRs for SARS-CoV-2 relative to CCC. CONCLUSIONS: Our data confirm, for what we believe is the first time, the existence of unique memory CD4(+) T cell clonotypes crossrecognizing SARS-CoV-2 and CCCs. The lower avidity of crossreactive TCRs for SARS-CoV-2 may be the result of antigenic imprinting, such that preexisting CCC-specific memory T cells have reduced expansive capacity upon SARS-CoV-2 infection. Further studies are needed to determine how these crossreactive T cell responses affect clinical outcomes in COVID-19 patients. FUNDING: NIH funding (U54CA260492, P30CA006973, P41EB028239, R01AI153349, R01AI145435-A1, R21AI149760, and U19A1088791) was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the National Institute of Biomedical Imaging and Bioengineering. The Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University Provost, and The Bill and Melinda Gates Foundation provided funding for this study. |
| Databáze: | OpenAIRE |
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