Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T- cell epitope of primary biliary cirrhosis

Shinji Shimoda, Minoru Nakamura, Hirohisa Shigematsu, Hironori Tanimoto, Toshihumi Gushima, M. Eric Gershwin, Hiromi Ishibashi

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Abstract

The human PDC-E2 163-176 peptide (GDLLAEIETDKATI) is an immunodominant autoreactive T-cell epitope in patients with primary biliary cirrhosis (PBC), restricted by HLA DRB4*0101. We have previously reported that the ExDK sequence is essential for recognition of this epitope and identified 1 mimicry peptide, Escherichia coli PDC-E2 peptide (EQSLITVEGDKASM), which can activate human PDC-E2 163-176 peptide-reactive T-cell clones. In the present study, to further investigate mimicry peptides possibly involved in PBC, we generated 13 different T-cell clones reactive to the human PDC-E2 163-176 peptide following repeated in vitro stimulation of peripheral T lymphocytes with the human PDC-E2 163-176 peptide (native peptide) and tested for the reactivity of these T-cell clones to 30 different mimicry peptides derived from various self- and nonself proteins that have an ExDK-sequence. We found 7 mimicry peptides derived from microbial proteins that can activate at least 1 of these T-cell clones; 7 of 7 T-cell clones from patients with PBC and 2 of 6 T-cell clones from healthy subjects were activated by at least 1 to 6 different mimicry peptides. Two of 6 T-cell clones from healthy subjects were activated by specific mimicry peptides more strongly than by the native peptide, and 2 of 6 T-cell clones from healthy subjects were not activated by any mimicry peptides tested. Thus, the pattern and degree of activation by mimicry peptides differed in each T-cell clone, indicating the presence of a diverse spectrum of autoreactive T cells that are reactive to a single minimal epitope of the human PDC-E2 163-176 peptide.

Original languageEnglish
Pages (from-to)1212-1216
Number of pages5
JournalHepatology
Volume31
Issue number6
DOIs
Publication statusPublished - Jan 1 2000

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Peptide T
Immunodominant Epitopes
T-Lymphocyte Epitopes
Biliary Liver Cirrhosis
Peptides
T-Lymphocytes
Clone Cells
Healthy Volunteers
HLA-DRB4 Chains
Epitopes

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Shimoda, S., Nakamura, M., Shigematsu, H., Tanimoto, H., Gushima, T., Gershwin, M. E., & Ishibashi, H. (2000). Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T- cell epitope of primary biliary cirrhosis. Hepatology, 31(6), 1212-1216. https://doi.org/10.1053/jhep.2000.8090

Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T- cell epitope of primary biliary cirrhosis. / Shimoda, Shinji; Nakamura, Minoru; Shigematsu, Hirohisa; Tanimoto, Hironori; Gushima, Toshihumi; Gershwin, M. Eric; Ishibashi, Hiromi.

In: Hepatology, Vol. 31, No. 6, 01.01.2000, p. 1212-1216.

Research output: Contribution to journalArticle

Shimoda, S, Nakamura, M, Shigematsu, H, Tanimoto, H, Gushima, T, Gershwin, ME & Ishibashi, H 2000, 'Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T- cell epitope of primary biliary cirrhosis', Hepatology, vol. 31, no. 6, pp. 1212-1216. https://doi.org/10.1053/jhep.2000.8090
Shimoda, Shinji ; Nakamura, Minoru ; Shigematsu, Hirohisa ; Tanimoto, Hironori ; Gushima, Toshihumi ; Gershwin, M. Eric ; Ishibashi, Hiromi. / Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T- cell epitope of primary biliary cirrhosis. In: Hepatology. 2000 ; Vol. 31, No. 6. pp. 1212-1216.
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AU - Tanimoto, Hironori

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AU - Gershwin, M. Eric

AU - Ishibashi, Hiromi

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N2 - The human PDC-E2 163-176 peptide (GDLLAEIETDKATI) is an immunodominant autoreactive T-cell epitope in patients with primary biliary cirrhosis (PBC), restricted by HLA DRB4*0101. We have previously reported that the ExDK sequence is essential for recognition of this epitope and identified 1 mimicry peptide, Escherichia coli PDC-E2 peptide (EQSLITVEGDKASM), which can activate human PDC-E2 163-176 peptide-reactive T-cell clones. In the present study, to further investigate mimicry peptides possibly involved in PBC, we generated 13 different T-cell clones reactive to the human PDC-E2 163-176 peptide following repeated in vitro stimulation of peripheral T lymphocytes with the human PDC-E2 163-176 peptide (native peptide) and tested for the reactivity of these T-cell clones to 30 different mimicry peptides derived from various self- and nonself proteins that have an ExDK-sequence. We found 7 mimicry peptides derived from microbial proteins that can activate at least 1 of these T-cell clones; 7 of 7 T-cell clones from patients with PBC and 2 of 6 T-cell clones from healthy subjects were activated by at least 1 to 6 different mimicry peptides. Two of 6 T-cell clones from healthy subjects were activated by specific mimicry peptides more strongly than by the native peptide, and 2 of 6 T-cell clones from healthy subjects were not activated by any mimicry peptides tested. Thus, the pattern and degree of activation by mimicry peptides differed in each T-cell clone, indicating the presence of a diverse spectrum of autoreactive T cells that are reactive to a single minimal epitope of the human PDC-E2 163-176 peptide.

AB - The human PDC-E2 163-176 peptide (GDLLAEIETDKATI) is an immunodominant autoreactive T-cell epitope in patients with primary biliary cirrhosis (PBC), restricted by HLA DRB4*0101. We have previously reported that the ExDK sequence is essential for recognition of this epitope and identified 1 mimicry peptide, Escherichia coli PDC-E2 peptide (EQSLITVEGDKASM), which can activate human PDC-E2 163-176 peptide-reactive T-cell clones. In the present study, to further investigate mimicry peptides possibly involved in PBC, we generated 13 different T-cell clones reactive to the human PDC-E2 163-176 peptide following repeated in vitro stimulation of peripheral T lymphocytes with the human PDC-E2 163-176 peptide (native peptide) and tested for the reactivity of these T-cell clones to 30 different mimicry peptides derived from various self- and nonself proteins that have an ExDK-sequence. We found 7 mimicry peptides derived from microbial proteins that can activate at least 1 of these T-cell clones; 7 of 7 T-cell clones from patients with PBC and 2 of 6 T-cell clones from healthy subjects were activated by at least 1 to 6 different mimicry peptides. Two of 6 T-cell clones from healthy subjects were activated by specific mimicry peptides more strongly than by the native peptide, and 2 of 6 T-cell clones from healthy subjects were not activated by any mimicry peptides tested. Thus, the pattern and degree of activation by mimicry peptides differed in each T-cell clone, indicating the presence of a diverse spectrum of autoreactive T cells that are reactive to a single minimal epitope of the human PDC-E2 163-176 peptide.

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