{"doi":"10.1101/2024.02.09.579465","title":"PINK1 is a target of T cell responses in Parkinson’s disease","abstract":"Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases such as multiple sclerosis (MS). Here, we explored whether additional autoantigenic targets of T cells in PD. We generated 15-mer peptide pools spanning several PD-related proteins implicated in PD pathology, including GBA, SOD1, PINK1, parkin, OGDH, and LRRK2. Cytokine production (IFNγ, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. This approach identified unique epitopes and their HLA restriction from the mitochondrial-associated protein PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells. The T cell reactivity was predominantly found in male patients with PD, which may contribute to the heterogeneity of PD. Identifying and characterizing PINK1 and other autoinflammatory targets may lead to antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for PD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484395,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1222509,"name":"T. Michaelis","orcid":null,"position":1,"is_corresponding":false},{"id":814851,"name":"João Rodrigues Lima-Júnior","orcid":null,"position":2,"is_corresponding":false},{"id":103777,"name":"April Frazier","orcid":"0000-0002-4722-7304","position":3,"is_corresponding":false},{"id":750102,"name":"Ngan K. Tran","orcid":"0000-0002-6106-2833","position":4,"is_corresponding":false},{"id":106289,"name":"Elizabeth J. Phillips","orcid":"0000-0002-7623-3383","position":5,"is_corresponding":false},{"id":11900,"name":"S. Mallal","orcid":"0000-0002-7036-1309","position":6,"is_corresponding":false},{"id":230246,"name":"Irene Litvan","orcid":"0000-0002-3485-3445","position":7,"is_corresponding":false},{"id":108600,"name":"Jennifer G. Goldman","orcid":"0000-0001-5014-7535","position":8,"is_corresponding":false},{"id":279481,"name":"Roy N. Alcalay","orcid":"0000-0002-5717-4875","position":9,"is_corresponding":false},{"id":55666,"name":"John Sidney","orcid":"0000-0002-0987-405X","position":10,"is_corresponding":false},{"id":230247,"name":"David Sulzer","orcid":"0000-0001-7632-0439","position":11,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":12,"is_corresponding":false},{"id":230241,"name":"Cecilia S. Lindestam Arlehamn","orcid":"0000-0001-7302-8002","position":13,"is_corresponding":false},{"id":279109,"name":"Gregory P. Williams","orcid":"0000-0001-9523-1781","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:07:38.055693Z","pmid":"38405939","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":[]}