The TCR repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse
Akul Singhania, John Pham, Rekha Dhanwani, April Frazier, Juliana Rezende Dutra, Karen Marder, Elizabeth J. Phillips, S. Mallal, Amy W. Amara, David G. Standaert, David Sulzer, Bjoern Peters, Alessandro Sette, Cecilia S. Lindestam Arlehamn
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.