{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin Z"],"funding":["Intramural NIH HHS","Medical Research Council","NCI NIH HHS"],"pagination":["1087-1097"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690437"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(7)"],"pubmed_abstract":["Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term 'functional SPs'. The single functional HLA-B SP, known as HLA-B/-21M, induced high HLA-E expression, but conferred the lowest receptor recognition. Consequently, HLA-B/-21M SP competes with other SPs for providing epitope to HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for reassessment of previous disease models involving HLA-B/-21M. Genetic population data indicate a positive correlation between frequencies of functional SPs in humans and corresponding cytomegalovirus mimics, suggesting a means for viral escape from host responses. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2-HLA-E interactions in disease resistance/susceptibility."],"journal":["Nature immunology"],"pubmed_title":["HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses."],"pmcid":["PMC10690437"],"funding_grant_id":["MR/M019837/1","75N91019D00024","ZIA BC010792"],"pubmed_authors":["Andresson T","Horowitz A","Das S","Hoelzemer A","Garcia-Beltran WF","Carrington M","Lin Z","Naranbhai V","Quastel M","Gillespie GM","Yuki Y","McMichael AJ","Bashirova AA","Akdag M","Garner L","Ojeda P","Kasprzak WK","Viard M","Beiersdorfer M"],"additional_accession":[]},"is_claimable":false,"name":"HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses.","description":"Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term 'functional SPs'. The single functional HLA-B SP, known as HLA-B/-21M, induced high HLA-E expression, but conferred the lowest receptor recognition. Consequently, HLA-B/-21M SP competes with other SPs for providing epitope to HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for reassessment of previous disease models involving HLA-B/-21M. Genetic population data indicate a positive correlation between frequencies of functional SPs in humans and corresponding cytomegalovirus mimics, suggesting a means for viral escape from host responses. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2-HLA-E interactions in disease resistance/susceptibility.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jul","modification":"2026-05-29T00:46:46.128Z","creation":"2025-04-05T11:45:29.016Z"},"accession":"S-EPMC10690437","cross_references":{"pubmed":["37264229"],"doi":["10.1038/s41590-023-01523-z"]}}