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Analysis of T‐cell receptor β of the T‐cell clones reactive to the human PDC‐E2 163‐176 peptide in the context of HLA‐DR53 in patients with primary biliary cirrhosis
Author(s) -
Ichiki Y,
Shimoda S,
Hara H,
Shigematsu H,
Nakamura M,
Hayashida K,
Ishibashi H,
Niho Y
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260326
Subject(s) - primary biliary cirrhosis , epitope , t cell , t cell receptor , context (archaeology) , immunology , human leukocyte antigen , biliary cirrhosis , medicine , biology , antigen , microbiology and biotechnology , autoimmune disease , antibody , immune system , paleontology
Abstract T‐cell‐mediated autoimmune mechanisms are considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). In the previous study, we identified the immunodominant T‐cell epitope on the E2 component of pyruvate dehydrogenase complex (PDC‐E2) in patients with PBC who have HLA‐DRB4*0101. In this report, we revealed that the frequency of the T cells reactive to the human PDC‐E2 163‐176 peptide is significantly increased in the peripheral blood of patients with PBC as compared with healthy subjects. We also confirmed that these T cells were all restricted with HLA‐DRB4*01 (DR53) by using HLA‐DR‐transfected L cells. These results together with the evidence that the immunodominant B‐cell epitope overlaps with the human T‐cell epitope of the PDC‐E2 antigen indicate that the T cells reactive to this epitope are closely associated with the pathogenesis of PBC at least in patients who have HLA‐DR53. Therefore, we analyzed the T‐cell receptor (TCR) Vβ sequence of the five different T‐cell clones and the three T‐cell clones derived from three patients with PBC and healthy subjects, respectively, which are reactive to the human PDC‐E2 163‐176 peptide in the context of HLA‐DR53. The Vβ‐ and the Jβ‐gene usages were diverse among the T‐cell clones (Vβ11‐Jβ1.4, Vβ8‐Jβ1.2, Vβ12‐Jβ2.1, Vβ10‐Jβ1.5, and Vβ20‐Jβ2.1) in patients with PBC. By contrast, in the third complementarity determining region (CDR3), G was frequently found and GXG or GXS motif was identified in all T‐cell clones. Moreover, RGXG motif was found in three clones generated from two patients. In healthy subjects, the Vβ‐ and the Jβ‐gene usages were also diverse, and GXG and RGXG motif were found. These results indicate that the T cells may recognize the ligand (the human PDC‐E2 163‐176 peptide/HLA‐DR53 complex) using the limited motif in the CDR3 region and that the design of CDR3‐specific immunotherapy would be possible using these motifs.