Promiscuous T cells selected by Escherichia coli: OGDC-E2 in primary biliary cirrhosis.
J Autoimmun
; 20(3): 255-63, 2003 May.
Article
in En
| MEDLINE
| ID: mdl-12753811
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acyltransferases
/
T-Lymphocytes
/
Escherichia coli
/
Liver Cirrhosis, Biliary
Type of study:
Etiology_studies
Limits:
Humans
Language:
En
Journal:
J Autoimmun
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2003
Document type:
Article
Affiliation country:
Japan
Country of publication:
United kingdom