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, Hong Sun, Simon Brackenridge, Xiaodong Zhuang, Peter A C Wing, Max Quastel, Lucy Walters, Lee Garner, Beibei Wang, Xuan Yao, Suet Ling Felce, Yanchun Peng, Shona Moore, Bas W A Peeters, Margarida Rei, Joao Canto Gomes, Ana Tomas, Andrew Davidson, Malcolm G Semple, Lance C W Turtle, Peter J M Openshaw, J Kenneth Baillie, Alexander J Mentzer, Paul Klenerman, ISARIC4C Investigators, Persephone Borrow, Tao Dong, Jane A McKeating, Geraldine M Gillespie, Andrew J McMichael
Science immunology 2023 Jun 30Pathogen-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.
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Hongbing Yang, Hong Sun, Simon Brackenridge, Xiaodong Zhuang, Peter A C Wing, Max Quastel, Lucy Walters, Lee Garner, Beibei Wang, Xuan Yao, Suet Ling Felce, Yanchun Peng, Shona Moore, Bas W A Peeters, Margarida Rei, Joao Canto Gomes, Ana Tomas, Andrew Davidson, Malcolm G Semple, Lance C W Turtle, Peter J M Openshaw, J Kenneth Baillie, Alexander J Mentzer, Paul Klenerman, ISARIC4C Investigators, Persephone Borrow, Tao Dong, Jane A McKeating, Geraldine M Gillespie, Andrew J McMichael. 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. 2023 Jun 30;8(84):eabl8881
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PMID: 37390223
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