The Functional Epitope of M3R that Interacts with SS IgG

Recent evidences suggest that autoantibodies directed against muscarinic type 3 receptor (M3R) may contribute to the development of sicca symptoms and autonomic dysfunction in patients with Sjogren's syndrome(SS). However, the precise epitope(s) of the autoantibodies involved in this process has not been identified. Objectives: In this experiment, we designed six synthetic peptides covering all the extracellular domains of M3R and examined which domains interact with IgG purified from the sera of SS patients (SS IgG). Methods: the surface plasmon resonance based-optical biosensor system. Results: We found that synthetic peptides corresponding to the first and the third extracellular loop of the M3R interact with SS IgG. However, the first peptide also interacted with the control IgG. The third peptide, but not the first peptide, interacted with carbachol, a M3R agonist. Furthermore, the inhibitory effect of SS IgG on the activation of M3R by carbachol was blocked by the pretreatment of the third peptide. Conclusion: Our data show that the 514 to 527 amino acid region of M3R corresponding to the sequence of the third peptide interact with the SS IgG. Acknowledgement: This work was supported by the Korea Research Foundation Grant funded by the korean Government (MOEHRD)(KRF-2005-015-E00207).