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1. TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitisResearch in context

Author

Ming Zheng, Xin Zhang, Yinghui Zhou, Juan Tang, Qing Han, Yang Zhang, Qingshan Ni, Gang Chen, Qingzhu Jia, Haili Yu, Siqi Liu, Elizabeth Robins, Ning Jenny Jiang, Ying Wan, Qi-Jing Li, Zhi-Nan Chen, and Ping Zhu

Subjects
Medicine, Medicine (General), R5-920
Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive. Methods: Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities. Findings: We found that disease progression is associated with both CD4+ and CD8+ T cell oligo-clonal expansion, which suggests that αβ T cell activation may mediate AS disease progression. By developing a bioinformatics platform to dissect antigen-specific responses, we discovered a cell population consisting of both CD4+ and CD8+ T cells expressing identical TCRs, herein termed CD4/8 T cells. CD4/8 clonotypes were highly enriched in the spondyloarthritic joint fluid of patients, and their expansion correlated with the activity of disease. Interpretation: These results provide evidence on the T cell clone side to reveal the potential role of CD4/8 T cells in the etiology of AS development. Keywords: Ankylosing spondylitis, Autoimmune disease, T cells, TCR repertoire, Human, Complementarity determining region 3

Published
2019
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2. TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis

Author

Gang Chen, Ying Wan, Ning Jenny Jiang, Qing Han, Ying-Hui Zhou, Juan Tang, Qingshan Ni, Ming Zheng, Ping Zhu, Si-Qi Liu, Haili Yu, Xin Zhang, Qingzhu Jia, Elizabeth Robins, Zhi-Nan Chen, Yang Zhang, and Qi-Jing Li

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, Research paper, Amino Acid Motifs, CD8-Positive T-Lymphocytes, SpA, spondyloarthropathies, Complementarity determining region 3, SJF, Spondyloarthritic Joint Fluid, 0302 clinical medicine, T-Lymphocyte Subsets, Autoimmune disease, education.field_of_study, TCR, T cell receptor, Repertoire, General Medicine, Immunohistochemistry, medicine.anatomical_structure, PBMC, peripheral blood mononuclear cells, 030220 oncology & carcinogenesis, Disease Susceptibility, CDR3, complementarity determining region 3, Ankylosing spondylitis, Human, Adult, ERAP1, endoplasmic reticulum aminopeptidase 1, Adolescent, T cell, Antigen presentation, Population, T cells, Receptors, Antigen, T-Cell, Human leukocyte antigen, Biology, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, medicine, Humans, Spondylitis, Ankylosing, Amino Acid Sequence, education, AS, ankylosing spondylitis, HLA, human leukocyte antigen, T-cell receptor, Complementarity Determining Regions, TCR repertoire, MS, Multiple Sclerosis, 030104 developmental biology, JIA, Juvenile Idiopathic Arthritis, OOF, out-of-frame, Immunology, biology.protein, GWASs, genome-wide association studies, CD8, Biomarkers
Abstract

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive. Methods Utilizing TCRβ repertoire sequencing and bioinformatics tools developed in house, we analyzed overall TCR repertoire structures and antigen-recognizing CDR3 motifs in AS patients with different disease activities. Findings We found that disease progression is associated with both CD4+ and CD8+ T cell oligo-clonal expansion, which suggests that αβ T cell activation may mediate AS disease progression. By developing a bioinformatics platform to dissect antigen-specific responses, we discovered a cell population consisting of both CD4+ and CD8+ T cells expressing identical TCRs, herein termed CD4/8 T cells. CD4/8 clonotypes were highly enriched in the spondyloarthritic joint fluid of patients, and their expansion correlated with the activity of disease. Interpretation These results provide evidence on the T cell clone side to reveal the potential role of CD4/8 T cells in the etiology of AS development.

Published
2019

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