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

tetano

Editor, Senior Moderator
Sci Immunol


. 2023 Jun 30;8(84):eabl8881.
doi: 10.1126/sciimmunol.abl8881. Epub 2023 Jun 30. HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation

Hongbing Yang[SUP] 1 2 [/SUP], Hong Sun[SUP] 1 2 3 [/SUP], Simon Brackenridge[SUP] 1 [/SUP], Xiaodong Zhuang[SUP] 4 [/SUP], Peter A C Wing[SUP] 2 4 [/SUP], Max Quastel[SUP] 1 [/SUP], Lucy Walters[SUP] 1 [/SUP], Lee Garner[SUP] 1 [/SUP], Beibei Wang[SUP] 2 5 [/SUP], Xuan Yao[SUP] 2 5 [/SUP], Suet Ling Felce[SUP] 2 [/SUP], Yanchun Peng[SUP] 5 [/SUP], Shona Moore[SUP] 6 [/SUP], Bas W A Peeters[SUP] 1 [/SUP], Margarida Rei[SUP] 7 [/SUP], Joao Canto Gomes[SUP] 8 9 [/SUP], Ana Tomas[SUP] 10 11 [/SUP], Andrew Davidson[SUP] 12 [/SUP], Malcolm G Semple[SUP] 6 13 [/SUP], Lance C W Turtle[SUP] 6 14 [/SUP], Peter J M Openshaw[SUP] 15 [/SUP], J Kenneth Baillie[SUP] 16 [/SUP], Alexander J Mentzer[SUP] 17 [/SUP], Paul Klenerman[SUP] 18 [/SUP]; ISARIC4C Investigators; Persephone Borrow[SUP] 1 [/SUP], Tao Dong[SUP] 2 5 [/SUP], Jane A McKeating[SUP] 2 4 [/SUP], Geraldine M Gillespie[SUP] 1 [/SUP], Andrew J McMichael[SUP] 1 [/SUP]



Affiliations
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.


 
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