Unknown

Dataset Information

0

A new clustering method identifies multiple sclerosis-specific T-cell receptors.


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 ?/?/?/? chains, TCR diversity, and V/J usage were determined by next-generation sequencing. TCR ? 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. TCR? and TCR? 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 (pcorr  = 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 peptides (CMV-TCR). MS Severity Score (MSSS) was lower in patients with CMV-TCR than in those without (P = 0.037). CMV-IgG-positivity was associated with lower MSSS in HLA-DRB1*04:05 carriers (P = 0.0053). HLA-DRB1*04:05-positive individuals demonstrated higher CMV-IgG titers than HLA-DRB1*04:05-negative individuals (P = 0.017). CMV-IgG-positive patients had more Tregs than CMV-IgG-negative patients (P = 0.054).

Interpretation

High TCR?/TCR? diversity, regardless of age, is characteristic of MS. Association of a CMV-recognizing TCR with mild disability indicates CMV's protective role in HLA-DRB1*04:05-positive MS.

SUBMITTER: Hayashi F 

PROVIDER: S-EPMC7818280 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

A new clustering method identifies multiple sclerosis-specific T-cell receptors.

Hayashi Fumie F   Isobe Noriko N   Glanville Jacob J   Matsushita Takuya T   Maimaitijiang Guzailiayi G   Fukumoto Shoko S   Watanabe Mitsuru M   Masaki Katsuhisa K   Kira Jun-Ichi JI  

Annals of clinical and translational neurology 20210105 1


<h4>Objective</h4>To characterize T-cell receptors (TCRs) and identify target epitopes in multiple sclerosis (MS).<h4>Methods</h4>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  ...[more]

Similar Datasets

| S-EPMC8491073 | biostudies-literature
| S-EPMC6278629 | biostudies-other
| S-EPMC4420287 | biostudies-literature
| S-EPMC3832895 | biostudies-literature
| S-EPMC4426681 | biostudies-literature
| S-EPMC4503875 | biostudies-literature
| S-EPMC8516708 | biostudies-literature
| S-EPMC3714200 | biostudies-literature
| S-EPMC6839873 | biostudies-literature
| S-EPMC8713784 | biostudies-literature