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

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 sp...

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Main Authors: Akul Singhania, John Pham, Rekha Dhanwani, April Frazier, Juliana Rezende Dutra, Karen S. Marder, Elizabeth Phillips, Simon Mallal, Amy W. Amara, David G. Standaert, David Sulzer, Bjoern Peters, Alessandro Sette, Cecilia S. Lindestam Arlehamn
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-79726-9
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author Akul Singhania
John Pham
Rekha Dhanwani
April Frazier
Juliana Rezende Dutra
Karen S. Marder
Elizabeth Phillips
Simon Mallal
Amy W. Amara
David G. Standaert
David Sulzer
Bjoern Peters
Alessandro Sette
Cecilia S. Lindestam Arlehamn
author_facet Akul Singhania
John Pham
Rekha Dhanwani
April Frazier
Juliana Rezende Dutra
Karen S. Marder
Elizabeth Phillips
Simon Mallal
Amy W. Amara
David G. Standaert
David Sulzer
Bjoern Peters
Alessandro Sette
Cecilia S. Lindestam Arlehamn
author_sort Akul Singhania
collection DOAJ
description 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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spelling doaj.art-318a19c555da466f96aa22f94ae2ea3c2022-12-21T20:28:34ZengNature PortfolioScientific Reports2045-23222021-01-0111111010.1038/s41598-020-79726-9The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverseAkul Singhania0John Pham1Rekha Dhanwani2April Frazier3Juliana Rezende Dutra4Karen S. Marder5Elizabeth Phillips6Simon Mallal7Amy W. Amara8David G. Standaert9David Sulzer10Bjoern Peters11Alessandro Sette12Cecilia S. Lindestam Arlehamn13Division of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDepartment of Neurology, Columbia University Medical CenterDepartment of Neurology, Columbia University Medical CenterInstitute for Immunology and Infectious Diseases, Murdoch UniversityInstitute for Immunology and Infectious Diseases, Murdoch UniversityDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, Columbia University Medical CenterDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyDivision of Vaccine Discovery, La Jolla Institute for ImmunologyAbstract 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.https://doi.org/10.1038/s41598-020-79726-9
spellingShingle Akul Singhania
John Pham
Rekha Dhanwani
April Frazier
Juliana Rezende Dutra
Karen S. Marder
Elizabeth Phillips
Simon Mallal
Amy W. Amara
David G. Standaert
David Sulzer
Bjoern Peters
Alessandro Sette
Cecilia S. Lindestam Arlehamn
The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
Scientific Reports
title The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
title_full The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
title_fullStr The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
title_full_unstemmed The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
title_short The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
title_sort tcr repertoire of α synuclein specific t cells in parkinson s disease is surprisingly diverse
url https://doi.org/10.1038/s41598-020-79726-9
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