The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse

A. Singhania; J. Pham; R. Dhanwani; A. Frazier; J. Rezende Dutra; K.S. Marder; E. Phillips; S. Mallal; A.W. Amara; D.G. Standaert; D. Sulzer; B. Peters; A. Sette; C.S. Lindestam Arlehamn

doi:10.1038/s41598-020-79726-9

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The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse

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The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse

A. Singhania, J. Pham, R. Dhanwani, A. Frazier, J. Rezende Dutra, K.S. Marder, E. Phillips, S. Mallal, A.W. Amara, D.G. Standaert, …

Scientific Reports, Vol.11(1), Art. 302

2021

DOI: https://doi.org/10.1038/s41598-020-79726-9

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Abstract

The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression.

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Title: The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
Authors/Creators: A. Singhania (Author/Creator) - La Jolla Institute for Immunology
J. Pham (Author/Creator) - La Jolla Institute for Immunology
R. Dhanwani (Author/Creator) - La Jolla Institute for Immunology
A. Frazier (Author/Creator) - La Jolla Institute for Immunology
J. Rezende Dutra (Author/Creator)
K.S. Marder (Author/Creator) - Columbia University Irving Medical Center
E. Phillips (Author/Creator) - Murdoch University
S. Mallal (Author/Creator) - Murdoch University
A.W. Amara (Author/Creator) - University of Alabama at Birmingham
D.G. Standaert (Author/Creator) - University of Alabama at Birmingham
D. Sulzer (Author/Creator) - Columbia University Irving Medical Center
B. Peters (Author/Creator) - La Jolla Institute for Immunology
A. Sette (Author/Creator) - University of California San Diego
C.S. Lindestam Arlehamn (Author/Creator)
Publication Details: Scientific Reports, Vol.11(1), Art. 302
Publisher: Springer Nature
Identifiers: 991005542707007891
Copyright: © 2021 Springer Nature Limited
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.127 T Cell Regulation
Web Of Science research areas: Immunology
ESI research areas: Immunology