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

Collapse authors list.
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) , Felce, Suet Ling, Peng, Yanchun, Moore, Shona ORCID: 0000-0001-8610-2806, Peeters, Bas WA, Rei, Margarida, Gomes, Joao Canto, Tomas, Ana G, Davidson, Andrew, Semple, Malcolm G ORCID: 0000-0001-9700-0418, Turtle, Lance CW ORCID: 0000-0002-0778-1693, Openshaw, Peter JMJ, Baillie, J Kenneth, Mentzer, Alexander J, Klenerman, Paul, Borrow, Persephone, Dong, Tao, McKeating, Jane A, Gillespie, Geraldine M and McMichael, Andrew J (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-.

PDF abl8881_CombinedPDF_v1[95131].pdf - Author Accepted Manuscript Download (5MB) | Preview

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.

Item Type:	Article
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:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3172979