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

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 fo...

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Bibliographic Details
Published in:Scientific reports 2021-01, Vol.11 (1), p.302-302, Article 302
Main Authors: Singhania, Akul, Pham, John, Dhanwani, Rekha, Frazier, April, Rezende Dutra, Juliana, Marder, Karen S., Phillips, Elizabeth, Mallal, Simon, Amara, Amy W., Standaert, David G., Sulzer, David, Peters, Bjoern, Sette, Alessandro, Lindestam Arlehamn, Cecilia S.
Format: Article
Language:English
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alpha-Synuclein - metabolism
Antigens
Autoantigens
Case-Control Studies
Epitopes
Female
Histocompatibility antigen HLA
Humanities and Social Sciences
Humans
Lymphocytes
Lymphocytes T
Male
Movement disorders
multidisciplinary
Neurodegenerative diseases
Parkinson Disease - immunology
Parkinson Disease - metabolism
Parkinson's disease
Pertussis
Receptors, Antigen, T-Cell - metabolism
Science
Science (multidisciplinary)
Synuclein
T cell receptors
T-Lymphocytes - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-79726-9