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EBioMedicine. 2019 Sep;47:414-426. doi: 10.1016/j.ebiom.2019.07.032. Epub 2019 Aug 30.

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

Author information

1
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China; Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China.
2
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
3
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China.
4
National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China.
5
Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China.
6
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
7
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
8
Biomedical Analysis Center, Third Military Medical University, Chongqing 400038, China. Electronic address: wanying.cn@gmail.com.
9
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: qi-jing.li@duke.edu.
10
National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: znchen@fmmu.edu.cn.
11
Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; National Translational Science Center for Molecular Medicine & Department of Cell Biology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: zhuping@fmmu.edu.cn.

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; Complementarity determining region 3; Human; T cells; TCR repertoire

PMID:
31477563
DOI:
10.1016/j.ebiom.2019.07.032
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