Functional role of M3 muscarinic acetylcholine receptor (M3R) reactive T cells and anti-M3R autoantibodies in patients with Sjögren's syndrome

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into the lachrymal and salivary glands, leading to dry eyes and mouth. Infiltration is also found in the kidneys, lungs, thyroid, and liver. Immunohistochemical studies have shown that most infiltrating lymphocytes are CD4⁺ T cell receptor (TCR) αβ T cells. The antigen specificity of T cells is decided by TCR expressed on T cells. The usage of TCRα and TCRβ genes have been examined by immunological and molecular biological methods. Autoantigens recognized by T cells infiltrating into salivary glands have been analyzed and several candidates for autoantigens have been clarified. In the present study, we focused on M3 muscarinic acetylcholine receptor (M3R) as a salivary gland-specific autoantigen and clarified T cell epitopes and B cell epitopes on M3R. The functions of anti-M3R antibodies and M3R reactive T cells were also carried out. To clarify whether M3R reactive T cells play a crucial role in the generation of autoimmune sialoadenitis, splenic CD3+T cells form M3R^-/- mice immunized by M3R peptides were transferred into Rag-1^-/- mice and sialoadenitis analyzed. The functional role of M3R reactive T cells in the generation of SS was also discussed.