ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

CD8+ T cells specific for an immunodominant SARS-CoV- 2 nucleocapsid epitope cross-react with selective seasonal coronaviruses (#298)

Emma J Grant 1 2 , Katie E Lineburg 3 , Srividhya Swaminathan 3 4 , Dimitra SM Chatzileontiadou 1 2 , Christopher Szeto 1 2 , Hannah Sloane 1 2 , Archana Panikkar 3 , Jyothy Raju 3 , Pauline Crooks 3 , Sweera Rehan 3 , Andrea T Nguyen 1 2 , Lea Lekieffre 3 , Michelle A Neller 3 , Zhen Wei Marcus Tong 5 , Dhilshan Jayasinghe 1 2 , Keng Yih Chew 4 , Christian A Lobos 1 2 , Hanim Halim 1 , Jacqueline M Burrows 3 , Alan Tunnicliffe-Riboldi 6 , Weisan Chen 2 , Lloyd D'Orsogna 7 8 , Rajiv Khanna 3 , Kirsty R Short 4 9 , Corey Smith 3 4 , Stephanie Gras 1 2
  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Victoria, Australia
  2. Infection and Immunity Program, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, 3086, Victoria, Australia
  3. Department of Immunology, QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Translational and Human Immunology Laboratory,QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  4. Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  5. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  6. Australian Synchrotron, ANSTO, Clayton 3168, Victoria, Australia
  7. Department of Clinical Immunology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Perth, Western Australia, Australia
  8. School of Medicine, University of Western Australia, Nedlands, Western Australia, Australia
  9. Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia

Significant efforts are being made worldwide to understand the immune response to SARS-CoV-2, responsible for the COVID-19 pandemic, including the role of preexisting T cell immunity. Understanding the mechanisms that promote cross-recognition by T cells induced by seasonal coronaviruses will be critical for future predictions on the role of pre-existing immunity in protection against severe disease. We demonstrate that the SARS-CoV-2 nucleocapsid (N) protein induces an immunodominant response in HLA-B7+ COVID-19-recovered individuals that is also readily detectable in unexposed donors. This immunodominant response is driven by a single N-encoded epitope that displays a high degree of conservation with the homologous region in circulating coronaviruses. We show that T cell-mediated cross-reactivity can be detected towards the circulating OC43/HKU-1 coronaviruses, but not the 229E or NL63 coronaviruses, due to different peptide conformations. This cross-reactivity is driven by private T cell receptor repertoires with a bias for TRBV27 and a long CDR3b loop in unexposed and COVID-19-recovered individuals. Together, our findings demonstrate the basis of pre-existing immunity to a conserved and highly immunogenic SARS-CoV-2 epitope driven by cross-reactive memory T cells, suggesting long-lived protective immunity.