Antigenic Epitopes on Human P-glycoprotein Recognized by Autoimmune Hepatitis Autoantibody as a Case Study

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概要

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• Multiple drug resistant protein 1 (MDR1), P-glycoprotein, plays a role in the blood-brain barrier, preventing drug distribution into the brain, and in cancer chemotherapy. MDR1 is composed of two repeated fragments and there are six transmembrane domain (TMD) on the N-terminal of each repeat and a nucleotide-binding domain (NBD) on the C-terminal. We reported that sera from autoimmune hepatitis patients well reacted with MDR1 by enzyme-linked immuno-sorbent assay (ELISA) [Shinoda et al, (2004) Autoimmunity, 37, 473-480]. In this study, to determine antigenic sites, peptides on the extra-cellular loop (ECL), TMD and NBD of MDR1 were applied to ELISA with sera from 4 autoimmune hepatitis (AIH) patients and 4 normal individuals. The results showed that serum from Patient 3 reacted well with peptide 314-328 and weakly with peptide 957-971. Meanwhile, serum from Patient 4 reacted well with peptide 850-857 and weakly with peptide 741-755 and 957-971. All the five peptides reacted with sera from Patients 3 and 4 were located on ECL. Normal sera did not react with those peptides and the reactions of sera from Patients 1 and 2 were marginal. Sera from 4 patients and normal individuals did not react with peptides of TMD and NBD. These results suggest that some ECL on MDR1 play a role of antigenic determinants, and TMD and NBD do not. Personal specificity and diversity of antibodies from the AIH patients (such as Patients 3 and 4) against antigenic determinant were found.

• 公益社団法人日本薬学会の論文
• 2007-06-01

著者

• Mizutani Takaharu

  Graduate School Of Pharmaceutical Sciences Nagoya City Univ.

• Masuda Masatoshi

  Graduate School of Pharmaceutical Sciences, Nagoya City University

• Masuda Masatoshi

  Graduate School Of Pharmaceutical Sciences Nagoya City University

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• Antigenic Epitopes on Human P-glycoprotein Recognized by Autoimmune Hepatitis Autoantibody as a Case Study

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