{"doi":"10.1084/jem.20221941","title":"Intracellular trafficking of HLA-E and its regulation","abstract":"Interest in MHC-E-restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)-restricted CD8+ T cell response requires an understanding of the pathway(s) of HLA-E transport and antigen presentation, which have not been clearly defined previously. We show here that, unlike classical HLA class I, which rapidly exits the endoplasmic reticulum (ER) after synthesis, HLA-E is largely retained because of a limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and is rapidly internalized. The cytoplasmic tail plays a crucial role in facilitating HLA-E internalization, which results in its enrichment in late and recycling endosomes. Our data reveal distinctive transport patterns and delicate regulatory mechanisms of HLA-E, which help to explain its unusual immunological functions.","journal":"The Journal of Experimental Medicine","year":2023,"id":321410,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":636327,"name":"Ester Gea‐Mallorquí","orcid":"0000-0002-6915-074X","position":1,"is_corresponding":false},{"id":857285,"name":"Huw Colin‐York","orcid":"0000-0002-6585-3237","position":2,"is_corresponding":false},{"id":857286,"name":"Marco Fritzsche","orcid":"0000-0002-8712-7471","position":3,"is_corresponding":false},{"id":447717,"name":"Geraldine M. Gillespie","orcid":"0000-0002-1075-870X","position":4,"is_corresponding":false},{"id":447715,"name":"Simon Brackenridge","orcid":"0000-0002-0587-7560","position":5,"is_corresponding":false},{"id":269955,"name":"Persephone Borrow","orcid":"0000-0002-3877-9780","position":6,"is_corresponding":false},{"id":106118,"name":"Andrew J. McMichael","orcid":"0000-0002-9101-7478","position":7,"is_corresponding":false},{"id":1033485,"name":"Wanlin He","orcid":"0000-0002-8117-9692","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37140910","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":[]}