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TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis
- Source :
- EBioMedicine
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....712dafb9b4b2513b4dd0bad09d7b6c47