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

Williams, G. P.; Michaelis, T.; Rodrigues Lima-Junior, J.; Frazier, A.; Tran, N. K.; Phillips, E. J.; Mallal, S. A.; Litvan, I.; Goldman, J. G.; Alcalay, R. N.; Sidney, J.; Sulzer, D.; Sette, A.; Lindestam Arlehamn, C. S.

doi:10.1101/2024.02.09.579465

bioRxiv · 10.1101/2024.02.09.579465

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

Williams, G. P.·Michaelis, T.·Rodrigues Lima-Junior, J.·Frazier, A.·Tran, N. K.·Phillips, E. J.·Mallal, S. A.·Litvan, I.·Goldman, J. G.·Alcalay, R. N.·Sidney, J.·Sulzer, D.·Sette, A.·Lindestam Arlehamn, C. S.

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Abstract

Parkinsons 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 (IFN{gamma}, 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.

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Williams, G. P., Michaelis, T., Rodrigues Lima-Junior, J., Frazier, A., Tran, N. K., Phillips, E. J., Mallal, S. A., Litvan, I., Goldman, J. G., Alcalay, R. N., Sidney, J., Sulzer, D., Sette, A., Lindestam Arlehamn, C. S.. 2024-02-12. PINK1 is a target of T cell responses in Parkinson's disease. https://doi.org/10.1101/2024.02.09.579465

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