1. CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses
- Author
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Lea Lekieffre, Zhen Wei Marcus Tong, Michelle A Neller, Jacqueline M. Burrows, Keng Yih Chew, Alan Riboldi-Tunnicliffe, Dhilshan Jayasinghe, Archana Panikkar, Kirsty R. Short, Jyothy Raju, Christopher Szeto, Andrea T. Nguyen, Emma J. Grant, Demetra S.M. Chatzileontiadou, Hanim Halim, Stephanie Gras, Sweera Rehan, Weisan Chen, Lloyd D'Orsogna, Corey Smith, Rajiv Khanna, Hannah Sloane, Srividhya Swaminathan, Katie E. Lineburg, Pauline Crooks, and Christian A. Lobos
- Subjects
Models, Molecular ,0301 basic medicine ,cross-reactivity ,viruses ,Immunology ,Receptors, Antigen, T-Cell ,Epitopes, T-Lymphocyte ,CD8-Positive T-Lymphocytes ,Cross Reactions ,Biology ,medicine.disease_cause ,Cross-reactivity ,Article ,immune response ,Epitope ,Virus ,HLA-B7 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,seasonal coronaviruses ,medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Amino Acid Sequence ,Peptide sequence ,Coronavirus ,Immunodominant Epitopes ,SARS-CoV-2 ,T-cell receptor ,COVID-19 ,virus diseases ,Virology ,HLA ,030104 developmental biology ,Infectious Diseases ,030220 oncology & carcinogenesis ,immunodominant epitope ,Peptides ,CD8+ T cell ,Immunologic Memory - Abstract
Efforts are being made worldwide to understand the immune response to SARS-CoV-2, the virus responsible for the COVID-19 pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity towards circulating OC43 and HKU-1 beta coronaviruses, but not 229E or NL63 alpha coronaviruses, due to different peptide conformations. TCR sequencing indicated cross-reactivity was driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3β loop. Together, our findings demonstrate the basis of selective T cell cross-reactivity towards an immunodominant SARS-CoV-2 epitope and its homologues from seasonal coronaviruses, suggesting long-lived protective immunity., Graphical Abstract, The impact of seasonal coronaviruses on immune responses to SARS-CoV-2 is an active area of research. Here, Lineburg et al identify CD8+ T cells specific for a conserved and immunodominant SARS-CoV-2 epitope in HLA-B7+ individuals. Furthermore, SARS-CoV-2 epitope-specific CD8+ T cells display cross-reactivity to beta but not alpha coronaviruses due to distinct peptide–HLA conformations.
- Published
- 2021