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. TurtlePeter J.M. Openshaw, J. Kenneth Baillie, Alexander J. Mentzer, Paul Klenerman, Persephone Borrow, Tao Dong, Jane A. McKeating, Geraldine M. Gillespie, Andrew J. McMichael

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Article numbereabl8881
Pages (from-to)eabl8881
JournalScience Immunology
Issue number84
Publication statusPublished - 30 Jun 2023


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