{"doi":"10.1101/2020.07.13.201079","title":"Overexpression of HLA class I predominantly on alpha cell in at risk individuals for type 1 diabetes","abstract":"Abstract Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study investigated the HLA-I expression in autoantibody positive (AAB+) donors and more closely defined its intra-islet and intracellular localization as well as proximity to infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I hyper-expression had already occurred prior to clinical diagnosis of T1D in islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was associated with intra-cellular accumulation in the Golgi. Proximity analysis showed a moderate but significant correlation between HLA-I and infiltrating CD8 T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not only demonstrate a very early, islet-intrinsic immune-independent increase of HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells in T1D. Summary Human leukocyte antigens of class-I (HLA-I) are hyper-expressed in insulin-containing islets of type 1 diabetic (T1D) donors. This study finds HLA-I hyper-expression occurs prior to clinical diagnosis of T1D in islets of autoantibody-positive donors and mostly expressed by alpha cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123880,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":568082,"name":"Somayeh Sabouri","orcid":null,"position":1,"is_corresponding":false},{"id":324391,"name":"William B. Kiosses","orcid":"0000-0003-1832-9050","position":2,"is_corresponding":false},{"id":436002,"name":"Sakthi Rajendran","orcid":"0000-0002-1603-9693","position":3,"is_corresponding":false},{"id":567478,"name":"Estefanía Quesada‐Masachs","orcid":"0000-0001-6033-1176","position":4,"is_corresponding":false},{"id":436004,"name":"Matthias von Herrath","orcid":"0000-0002-5211-0485","position":5,"is_corresponding":false},{"id":567477,"name":"Mehdi A. Benkahla","orcid":"0000-0002-5207-8390","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"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":[]}