{"doi":"10.1111/imr.13434","title":"<scp>HLA</scp>‐E: Immune Receptor Functional Mechanisms Revealed by Structural Studies","abstract":"HLA-E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x-CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism. A second minor function is to present other, weaker binding, pathogen-derived peptides to T lymphocytes. Most of these peptides bind suboptimally to HLA-E, but this binding appears to be enabled by the relative stability of peptide-free, but receptive, HLA-E-β2m complexes. This, in turn, may favor nonclassical antigen processing that may be associated with bacteria infected cells. This review explores how the structure of HLA-E, bound to different peptides and then to NKG2-CD94 or T-cell receptors, relates to HLA-E cell biology and immunology. A detailed understanding of this molecule could open up opportunities for development of universal T-cell and NK-cell-based immunotherapies.","journal":"Immunological Reviews","year":2025,"id":509958,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9451,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":585863,"name":"Max Quastel","orcid":"0000-0001-6551-4713","position":1,"is_corresponding":false},{"id":106118,"name":"Andrew J. McMichael","orcid":"0000-0002-9101-7478","position":2,"is_corresponding":false},{"id":447717,"name":"Geraldine M. Gillespie","orcid":"0000-0002-1075-870X","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"39753525","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}