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A new clustering method identifies multiple sclerosis‐specific T‐cell receptors by Hayashi, Fumie ;Isobe, Noriko ;Glanville, Jacob ;Matsushita, Takuya ;Maimaitijiang, Guzailiayi ;Fukumoto, Shoko ;Watanabe, Mitsuru ;Masaki, Katsuhisa ;Kira, Jun‐ichi is a Medicine article available to read on EtoBox.

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## Abstract ## Objective To characterize T‐cell receptors (TCRs) and identify target epitopes in multiple sclerosis (MS). ## Methods Peripheral blood mononuclear cells were obtained from 39 MS patients and 19 healthy controls (HCs). TCR repertoires for α/β/δ/γ chains, TCR diversity, and V/J usage were determined by next‐generation sequencing. TCR β chain repertoires were compared with affectation status using a novel clustering method, Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH). Cytomegalovirus (CMV)‐IgG was measured in an additional 113 MS patients and 93 HCs. Regulatory T cells (Tregs) were measured by flow cytometry. ## Results TCR diversity for all four chains decreased with age. TCRα and TCRβ diversity was higher in MS patients (__P__ = 0.0015 and 0.024, respectively), even after age correction. __TRAJ56__ and __TRBV4‐3__ were more prevalent in MS patients than in HCs (__p^corr^__ = 0.027 and 0.040, respectively). GLIPH consolidated 208,674 TCR clones from MS patients into 1,294 clusters, among which two candidate clusters were identified. The __TRBV4‐3__ cluster was shared by __HLA‐DRB1\*04:05__‐positive patients (87.5%) and predicted to recognize CMV pe

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Author
Hayashi, Fumie ;Isobe, Noriko ;Glanville, Jacob ;Matsushita, Takuya ;Maimaitijiang, Guzailiayi ;Fukumoto, Shoko ;Watanabe, Mitsuru ;Masaki, Katsuhisa ;Kira, Jun‐ichi
Publisher
Wiley
Published
2021
Language
EN
Field
Medicine (Health Sciences)

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