Yang, Hongbing, Sun, Hong, Brackenridge, Simon, Zhuang, Xiaodong, Wing, Peter AC, Quastel, Max, Walters, Lucy, Garner, Lee, Wang, Beibei, Yao, Xuan et al (show 19 more authors)
(2023)
HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation.
SCIENCE IMMUNOLOGY, 8 (84).
eabl8881-.
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Abstract
Pathogen-specific CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cells. HLA-E peptide-specific CD8<sup>+</sup> 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.
Item Type: | Article |
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Uncontrolled Keywords: | ISARIC4C Investigators, CD8-Positive T-Lymphocytes, Humans, Antibodies, Histocompatibility Antigens Class II, Virus Replication, Down-Regulation, COVID-19, SARS-CoV-2, HLA-E Antigens |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 22 Sep 2023 15:21 |
Last Modified: | 05 Jan 2024 06:44 |
DOI: | 10.1126/sciimmunol.abl8881 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3172979 |