Analysis of T cell autoepitope in primary biliary cirrhosis

H. Ishibashi, S. Shimoda, M. Nakamura, K. Hayashida, Y. Niho

Research output: Contribution to journalArticle

Abstract

We established six T cell clones specific for PDC-E2 peptides from four different patients with PBC using 33 different peptides of 17-20 amino acid residues corresponding to human PDC-E2 as stimulating antigens (Ags). The minimal T cell epitopes of these six T cell clones were all mapped to the same region of the PDC-E2 peptide 163-176 (GDLLAEIETDKATI), which corresponds to the inner lipoyl domain of PDC-E2. The HLA restriction molecules for this epitope were all identified as HLA DR53 (B1*0101). The common essential amino acids of this epitope for these T cell clones were E, D and K at positions 170, 172 and 173, respectively, whereas other crucial amino acids for this epitope differed in each T cell clone. In addition, the alanine substituted peptides at positions 170 and 173, but not 172, inhibited the proliferation of all T cell clones induced by the original peptide of human PDC-E2 163-176, indicating that amino acid D at position 172 is a critical MHC binding site for all T cell clones tested. Interestingly, all T cell clones reacted to the PDC-E2 peptide 36-49 (GDLIAEVETDKATV), which corresponds to the outer lipoyl domain of human PDC-E2. Furthermore, one T cell clone cross reacted to exogenous Ag, such as E. coli PDC-E2 peptide 31- 44/134 147/235-248 (EQSLITVEGDKASM), which has an EXDK sequence. This is a difinite demonstration of the presence of molecular mimicry at the T cell clonal level in human autoimmune diseases. It is also considered possible to design a peptide-specific immunotherapy based on the findings of T cell autoepitopes in PBC.

Original languageEnglish
Pages (from-to)1272-1279
Number of pages8
JournalBiotherapy
Volume10
Issue number10
Publication statusPublished - Jan 1 1996

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ishibashi, H., Shimoda, S., Nakamura, M., Hayashida, K., & Niho, Y. (1996). Analysis of T cell autoepitope in primary biliary cirrhosis. Biotherapy, 10(10), 1272-1279.