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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/318a19c555da466f96aa22f94ae2ea3c
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spelling	oai:doaj.org-article:318a19c555da466f96aa22f94ae2ea3c2021-12-02T14:01:37ZThe TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse10.1038/s41598-020-79726-92045-2322https://doaj.org/article/318a19c555da466f96aa22f94ae2ea3c2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79726-9https://doaj.org/toc/2045-2322Abstract 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.Akul SinghaniaJohn PhamRekha DhanwaniApril FrazierJuliana Rezende DutraKaren S. MarderElizabeth PhillipsSimon MallalAmy W. AmaraDavid G. StandaertDavid SulzerBjoern PetersAlessandro SetteCecilia S. Lindestam ArlehamnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	tcr repertoire of α-synuclein-specific t cells in parkinson’s disease is surprisingly diverse
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/318a19c555da466f96aa22f94ae2ea3c
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The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse

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