Prediction and identification of autoepitopes of PDC-E2 specific CD8+ CTL in primary biliary cirrhosis patients.
- Author:
Hai-ying LIU
1
;
Ding-kang YAO
;
Xiao-qing TU
;
Ye ZHOU
;
Ye ZHU
;
Yan CHEN
;
Lie-ying FAN
;
Ren-qian ZHONG
Author Information
- Publication Type:Journal Article
- MeSH: Antibody-Producing Cells; cytology; Autoantigens; immunology; Autoimmunity; CD8-Positive T-Lymphocytes; cytology; immunology; metabolism; Cell Line; Dihydrolipoyllysine-Residue Acetyltransferase; Epitope Mapping; Epitopes, T-Lymphocyte; immunology; HLA-A Antigens; immunology; HLA-A2 Antigen; Humans; Liver Cirrhosis, Biliary; enzymology; genetics; immunology; Phenotype; Protein Binding; Pyruvate Dehydrogenase Complex; genetics; immunology; metabolism; T-Lymphocytes, Cytotoxic; immunology
- From: Acta Academiae Medicinae Sinicae 2004;26(5):500-504
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo identify autoepitopes of E2 subunit of pyruvate dehydrogenase complex (PDC-E2) specific CD8+ CTL in primary biliary cirrhosis (PBC) patients.
METHODSAn online database SYFPEITHI was applied to predict HLA-A*0201 restricted epitopes which located in PDC-E2 30-50 aa and 150-190 aa where B-cell epitopes clustered with CD4+ T-cell epitopes. T2 cell line reconstitution and stabilization assay, induction of specific CTL lines from peripheral blood mononuclear cells (PBMCs) of patients with PBC and cytotoxicity of peptides-induced CTL were performed to screen the epitopes from those candidates.
RESULTSFive potential epitopes were predicted by database. Of the 5 candidates, two peptides 159-167 aa and 165-174 aa, with highly binding activity to HLA-A*0201 molecules, could stimulate PBMCs from most HLA-A*0201 positive PBC patients to proliferate and peptide-induced CTL lines showed specific cytotoxicity.
CONCLUSIONPeptides of KLSEGDLLA (159-167 aa) and LLAEIETDKA (165-174 aa) in the inner lipoyl domain of PDC-E2 are HLA-A*0201 restricted CD8+ CTL immunodominant epitopes in PBC.