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HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation

Abstract:
Pathogen-specific CD8+ T cell responses restricted by the nonpolymorphic nonclassical class Ib molecule human leukocyte antigen E (HLA-E) are rarely reported in viral infections. The natural HLA-E ligand is a signal peptide derived from classical class Ia HLA molecules that interact with the NKG2/CD94 receptors to regulate natural killer cell functions, but pathogen-derived peptides can also be presented by HLA-E. Here, we describe five peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that elicited HLA-E–restricted CD8+ T cell responses in convalescent patients with coronavirus disease 2019. These T cell responses were identified in the blood at frequencies similar to those reported for classical HLA-Ia–restricted anti–SARS-CoV-2 CD8+ T cells. HLA-E peptide–specific CD8+ T cell clones, which expressed diverse T cell receptors, suppressed SARS-CoV-2 replication in Calu-3 human lung epithelial cells. SARS-CoV-2 infection markedly down-regulated classical HLA class I expression in Calu-3 cells and primary reconstituted human airway epithelial cells, whereas HLA-E expression was not affected, enabling T cell recognition. Thus, HLA-E–restricted T cells could contribute to the control of SARS-CoV-2 infection alongside classical T cells.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/sciimmunol.abl8881

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
ORCID:
0000-0002-0587-7560
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author
ORCID:
0000-0002-2354-3281


More from this funder
Grant:
215091/Z/18/Z
Grant:
222426/Z/21/Z
Grant:
200838/Z/16/Z


Publisher:
American Association for the Advancement of Science
Journal:
Science Immunology More from this journal
Volume:
8
Issue:
84
Article number:
eabl8881
Place of publication:
United States
Publication date:
2023-06-30
Acceptance date:
2023-06-07
DOI:
ISSN:
2470-9468
Pmid:
37390223


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