[Prediction and identification of autoepitopes of PDC-E2 specific CD8+ CTL in primary biliary cirrhosis patients].
OBJECTIVE
To identify autoepitopes of E2 subunit of pyruvate dehydrogenase complex (PDC-E2) specific CD8+ CTL in primary biliary cirrhosis (PBC) patients.


METHODS
An 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.


RESULTS
Five 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.


CONCLUSIONS
Peptides 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.
Liu
Hai-ying
HY
Department of Experimental Diagnosis, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Yao
Ding-kang
DK
Tu
Xiao-qing
XQ
Zhou
Ye
Y
Zhu
Ye
Y
Chen
Yan
Y
Fan
Lie-ying
LY
Zhong
Ren-qian
RQ
D000921:Antibody-Producing Cells / Q000166:cytology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D011485:Protein Binding; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D011768:Pyruvate Dehydrogenase Complex; D051047:Dihydrolipoyllysine-Residue Acetyltransferase