High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation

Nature Communications

Article

Lee Garner¹  Geraldine M. Gillespie¹  Andrew J. McMichael¹  Timo Rückert²  Chiara Romagnani³  Brooke D. Huisman⁴  Ning Guan⁴  Michael E. Birnbaum⁵  Nishant K. Singh⁶ 

[1] Centre for Immuno-Oncology, Old Road Campus Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK;Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Leibniz Institut, Berlin, Germany;Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Leibniz Institut, Berlin, Germany;Charité - Universitätsmedizin Berlin, Berlin, Germany;Koch Institute for Integrative Cancer Research, Cambridge, MA, USA;Department of Biological Engineering, MIT, Cambridge, MA, USA;Koch Institute for Integrative Cancer Research, Cambridge, MA, USA;Department of Biological Engineering, MIT, Cambridge, MA, USA;Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA;Koch Institute for Integrative Cancer Research, Cambridge, MA, USA;Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA;

关键词: ;   

DOI  :  10.1038/s41467-023-40220-1

 received in 2022-09-23, accepted in 2023-07-13,  发布年份 2023

来源: Springer

【 摘 要 】

HLA-E is a non-classical class I MHC protein involved in innate and adaptive immune recognition. While recent studies have shown HLA-E can present diverse peptides to NK cells and T cells, the HLA-E repertoire recognized by CD94/NKG2x has remained poorly defined, with only a limited number of peptide ligands identified. Here we screen a yeast-displayed peptide library in the context of HLA-E to identify 500 high-confidence unique peptides that bind both HLA-E and CD94/NKG2A or CD94/NKG2C. Utilizing the sequences identified via yeast display selections, we train prediction algorithms and identify human and cytomegalovirus (CMV) proteome-derived, HLA-E-presented peptides capable of binding and signaling through both CD94/NKG2A and CD94/NKG2C. In addition, we identify peptides which selectively activate NKG2C+ NK cells. Taken together, characterization of the HLA-E-binding peptide repertoire and identification of NK activity-modulating peptides present opportunities for studies of NK cell regulation in health and disease, in addition to vaccine and therapeutic design.

【 授权许可】

CC BY   
© Springer Nature Limited 2023. corrected publication 2023

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