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

Yasunori Ichiki, Shinji Shimoda, Hideo Hara, Hirohisa Shigematsu, Minoru Nakamura, Kazuhiro Hayashida, Hiromi Ishibashi, Yoshiyuki Niho

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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 HLADRB4*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 GX8 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.

Original languageEnglish
Pages (from-to)728-733
Number of pages6
JournalHepatology
Volume26
Issue number3
DOIs
Publication statusPublished - Jan 1 1997

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Biliary Liver Cirrhosis
T-Cell Antigen Receptor
Clone Cells
T-Lymphocytes
Peptides
Immunodominant Epitopes
Healthy Volunteers
T-Lymphocyte Epitopes
HLA-DRB4 Chains
Dihydrolipoyllysine-Residue Acetyltransferase
Complementarity Determining Regions
B-Lymphocyte Epitopes
HLA-DR53
HLA-DR Antigens
Immunotherapy
Genes
Epitopes
Ligands

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

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. / Ichiki, Yasunori; Shimoda, Shinji; Hara, Hideo; Shigematsu, Hirohisa; Nakamura, Minoru; Hayashida, Kazuhiro; Ishibashi, Hiromi; Niho, Yoshiyuki.

In: Hepatology, Vol. 26, No. 3, 01.01.1997, p. 728-733.

Research output: Contribution to journalArticle

Ichiki, Yasunori ; Shimoda, Shinji ; Hara, Hideo ; Shigematsu, Hirohisa ; Nakamura, Minoru ; Hayashida, Kazuhiro ; Ishibashi, Hiromi ; Niho, Yoshiyuki. / 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. In: Hepatology. 1997 ; Vol. 26, No. 3. pp. 728-733.
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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 HLADRB4*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 GX8 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.",
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