Promiscuous T cells selected by Escherichia coli: OGDC-E2 in primary biliary cirrhosis
| Autor: | Mine Harada, Akira Kawano, Hiromi Ishibashi, Sho Matsushita, Hironori Tanimoto, Shinji Shimoda, M. Eric Gershwin, Takashi Kamihira, Minoru Nakamura |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
T-Lymphocytes
T cell Immunology Pyruvate Dehydrogenase Complex Cross Reactions In Vitro Techniques Biology Dihydrolipoyllysine-Residue Acetyltransferase Lymphocyte Activation medicine.disease_cause Autoantigens Cross-reactivity Primary biliary cirrhosis Immune system Antigen Escherichia coli medicine Humans Immunology and Allergy Amino Acid Sequence Escherichia coli Infections Antigens Bacterial Immunodominant Epitopes Liver Cirrhosis Biliary Molecular Mimicry medicine.disease Peptide Fragments digestive system diseases Mitochondria Molecular mimicry medicine.anatomical_structure Bacterial antigen Acyltransferases |
| Zdroj: | Journal of Autoimmunity. 20:255-263 |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/s0896-8411(03)00024-6 |
| Popis: | The etiology of primary biliary cirrhosis (PBC) remains enigmatic. One theory that has attracted attention proposes that PBC is induced via molecular mimicry with Escherichia coli. If molecular mimicry is responsible for the immunogenic response in PBC, then T cell clones specific for E. coli antigens should stimulate and be cross-reactive with peptides specific for the human immunodominant autoepitopes. To address this issue, we developed T cell clones specific for E. coli OGDC-E2 peptide. Importantly, we demonstrate the presence of T cell clones specific for E. coli OGDC-E2 that react promiscuously with the human mitochondrial equivalents. Indeed, there was a significant increase in the liver derived T cell precursor frequency of such reactivity and such liver clones were only found in patients with PBC. In conclusion, these data suggest that PBC is a multi-hit disease involving a genetic predisposition, a mucosal response, and activation of promiscuous T cells; such activation may occur either directly from bacterial antigens, or indirectly through chemically-modified bacterial antigens. Dissection of the mechanisms involved will lead not only to understanding the immunogenetic basis of PBC, but likely its pathogenic etiology. |
| Databáze: | OpenAIRE |
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