PINK1 is a target of T cell responses in Parkinson’s disease

Gregory P. Williams; Antoine Freuchet; Tanner Michaelis; April Frazier; Ngan K. Tran; João Rodrigues Lima-Junior; Elizabeth J. Phillips; Simon A. Mallal; Irene Litvan; Jennifer G. Goldman; Roy N. Alcalay; John Sidney; David Sulzer; Alessandro Sette; Cecilia S. Lindestam Arlehamn

doi:10.1172/JCI180478

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PINK1 is a target of T cell responses in Parkinson’s disease

Journal article

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PINK1 is a target of T cell responses in Parkinson’s disease

Gregory P. Williams, Antoine Freuchet, Tanner Michaelis, April Frazier, Ngan K. Tran, João Rodrigues Lima-Junior, Elizabeth J. Phillips, Simon A. Mallal, Irene Litvan, Jennifer G. Goldman, …

The Journal of clinical investigation, Vol.135(4), e180478

2024

DOI: https://doi.org/10.1172/JCI180478

PMID: 39688918

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Abstract

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. While there is no curative treatment, the immune system’s involvement with autoimmune T cells that recognize the protein α-synuclein (α-syn) in a subset of individuals suggests new areas for therapeutic strategies. As not all patients with PD have T cells specific for α-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 β 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-γ, 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. PINK1, a mitochondrial-associated protein, has been identified as an autoantigen targeted by T cells from patients with Parkinson’s disease. This reactivity was predominantly found in male patients with Parkinson’s Disease, which may contribute to the heterogeneity of PD.

Details

Title: PINK1 is a target of T cell responses in Parkinson’s disease
Authors/Creators: Gregory P. Williams
Antoine Freuchet - La Jolla Institute for Immunology
Tanner Michaelis
April Frazier
Ngan K. Tran
João Rodrigues Lima-Junior
Elizabeth J. Phillips - Vanderbilt University
Simon A. Mallal - Vanderbilt University
Irene Litvan - National Institutes of Health
Jennifer G. Goldman
Roy N. Alcalay
John Sidney
David Sulzer - Research Network (United States)
Alessandro Sette
Cecilia S. Lindestam Arlehamn
Publication Details: The Journal of clinical investigation, Vol.135(4), e180478
Publisher: American Society for Clinical Investigation
Grant note: R01NS095435 / ; T32AI125179 / NIH N/A / WHAM Investigator’s fund ASAP-000375 / Alingning Science Across Parkinson’s
Identifiers: 991005743939307891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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