Isolation of Potential Pathogenic TCR ?chain Genes in Myasthenia Gravis Patients
Date Issued
2004
Date
2004
Author(s)
WANG, SHUI-HUA
DOI
zh-TW
Abstract
Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibody against acetylcholine receptor (AchR). These antibodies blocked the signal transduction between neuromuscular junctions and resulted in muscle weakness. In this study, we analyzed the Vδ5- and V?-containing T cell receptor (TCR) ?chain gene usages, and the nucleotide sequences of the CDR3 region in MG patients and healthy controls. The aim is to find potential pathogenic T cells to aid the development of specific therapy for the disease of myasthenia gravis.
In the study, cDNA of peripheral blood lymphocytes (PBLs) were made from four MG patients & three healthy controls (HCs). Additionally, the thymus and thyroid surgically removed and obtained from one of the MG patients were also included in this study. TCR genes carrying Vδ5 or V? were specifically amplified from cDNA by C?specific primer paired with Vδ5- and V?- specific primers, respectively. The PCR products were then subcloned and sequenced to analyze the nucleotide sequences of the CDR3 region.
First of all, in the Vδ5-C?gene usage, we observed a significant differential usage on TCRs with charged amino acids on the sixth or seventh position of the CDR3 region between patients and healthy controls. This result unexpectedly correlates well with the data obtained from experimental autoimmune myasthenia gravis (EAMG) and strongly indicates these TCRs are related to the development of the MG.
Second of all, in the V?-C?gene usage, there were no significant sequence differences in the CDR3 region between MG patients and the HC, except MG-Ⅳ, which did not use invariant TCR bearing V? sequences in our data. In addition, we also found a new third invariant TCR ?chain in human—V?-J?2-C? This type of TCR was detected as an expanded population in CD4+CD8+ DP T cells from one of the MG patients.
We believe that our data do shed light on understanding the TCR usage in MG patients and the potential pathogenic TCRs. Generating mice carrying our TCR ?chain sequences is the next step in order to confirm the role of the T cells bearing our TCRs. To help developing the specific therapy to medicate myasthenia gravis will be our final goal.
Subjects
自體免疫疾病
肌無力
T細胞接受器
Autoimmune disease
Myasthenia Gravis
T cell receptor
SDGs
Type
other
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