Ablation of CD8+ T cell recognition of an immunodominant epitope in SARS-CoV-2 Omicron variants BA.1, BA.2 and BA.3

Srividhya Swaminathan, Katie E. Lineburg, Archana Panikkar, Jyothy Raju, Lawton D. Murdolo, Christopher Szeto, Pauline Crooks, Laetitia Texier, Sweera Rehan, Michael J. Dewar-Oldis, Peter J. Barnard, George R. Ambalathingal, Michelle A. Neller, Kirsty R. Short, Stephanie Gras, Rajiv Khanna and Corey Smith ()
Additional contact information
Srividhya Swaminathan: QIMR Berghofer Medical Research Institute
Katie E. Lineburg: QIMR Berghofer Medical Research Institute
Archana Panikkar: QIMR Berghofer Medical Research Institute
Jyothy Raju: QIMR Berghofer Medical Research Institute
Lawton D. Murdolo: La Trobe University
Christopher Szeto: La Trobe University
Pauline Crooks: QIMR Berghofer Medical Research Institute
Laetitia Texier: QIMR Berghofer Medical Research Institute
Sweera Rehan: QIMR Berghofer Medical Research Institute
Michael J. Dewar-Oldis: La Trobe University
Peter J. Barnard: La Trobe University
George R. Ambalathingal: QIMR Berghofer Medical Research Institute
Michelle A. Neller: QIMR Berghofer Medical Research Institute
Kirsty R. Short: The University of Queensland
Stephanie Gras: La Trobe University
Rajiv Khanna: QIMR Berghofer Medical Research Institute
Corey Smith: QIMR Berghofer Medical Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-6

Abstract: Abstract The emergence of the SARS-CoV-2 Omicron variant has raised concerns of escape from vaccine-induced immunity. A number of studies have demonstrated a reduction in antibody-mediated neutralization of the Omicron variant in vaccinated individuals. Preliminary observations have suggested that T cells are less likely to be affected by changes in Omicron. However, the complexity of human leukocyte antigen genetics and its impact upon immunodominant T cell epitope selection suggests that the maintenance of T cell immunity may not be universal. In this study, we describe the impact that changes in Omicron BA.1, BA.2 and BA.3 have on recognition by spike-specific T cells. These T cells constitute the immunodominant CD8+ T cell response in HLA-A*29:02+ COVID-19 convalescent and vaccinated individuals; however, they fail to recognize the Omicron-encoded sequence. These observations demonstrate that in addition to evasion of antibody-mediated immunity, changes in Omicron variants can also lead to evasion of recognition by immunodominant T cell responses.

Date: 2022
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DOI: 10.1038/s41467-022-34180-1

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