{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:25:07Z","timestamp":1791498307446,"version":"4.3.4"},"reference-count":76,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alingning Science Across Parkinson\u2019s","award":["ASAP-000375"],"award-info":[{"award-number":["ASAP-000375"]}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS095435"],"award-info":[{"award-number":["R01NS095435"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["T32AI125179"],"award-info":[{"award-number":["T32AI125179"]}]},{"name":"WHAM Investigator\u2019s fund","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,17]]},"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second most prevalent neurodegenerative disorder. While there is no curative treatment, the immune system\u2019s involvement with autoimmune T cells that recognize the protein \u03b1-synuclein (\u03b1-syn) in a subset of individuals suggests new areas for therapeutic strategies. As not all patients with PD have T cells specific for \u03b1-syn, we explored additional autoantigenic targets of T cells in PD. We generated 15-mer peptides spanning several PD-related proteins implicated in PD pathology, including glucosylceramidase \u03b2 1 (GBA), superoxide dismutase 1 (SOD1), PTEN induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (parkin), oxoglutarate dehydrogenase (OGDH), and leucine rich repeat kinase 2 (LRRK2). Cytokine production (IFN-\u03b3, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. We identified PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells, as well as its unique epitopes, and their HLA restriction. The PINK1-specific T cell reactivity revealed sex-based differences, as it 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.<\/jats:p>","DOI":"10.1172\/jci180478","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T12:00:28Z","timestamp":1734436828000},"source":"Crossref","is-referenced-by-count":28,"title":["PINK1 is a target of T cell responses in Parkinson\u2019s disease"],"prefix":"10.1172","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9523-1781","authenticated-orcid":true,"given":"Gregory P.","family":"Williams","sequence":"first","affiliation":[{"name":"Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, California, USA."},{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network, Chevy Chase, Maryland, 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