Analysis of function of misfolded proteins presented on MHC class II molecules.

MHC II类分子通过向T细胞呈递肽抗原在免疫应答中发挥重要作用。然而，我们发现MHC II类分子将细胞错误折叠的蛋白质转运到细胞表面，而不加工成肽。因此，我们在本研究中分析了MHC II类分子转运到细胞表面的错误折叠蛋白的功能。我们发现在MHC II类分子上呈递的蛋白质有效地刺激抗原特异性B细胞。虽然MHC II类分子被认为是向T细胞呈递肽抗原，但我们的研究结果表明MHC II类分子可以向B细胞呈递蛋白抗原。此外，当我们分析自身免疫患者的自身抗体时，我们发现MHC II类分子上的蛋白质被自身抗体特异性识别。这些发现提示在MHC II类分子上异常呈现的错误折叠蛋白是一种靶向自身免疫性疾病。

MHC class II molecules play an important role in immune response by presenting peptide antigens to T cells. However, we found that MHC class II molecules transport cellular misfolded proteins to the cell surface without processing to peptides. Therefore, we analyzed functions of misfolded proteins transported to the cell surface by MHC class II molecules in this study. We found that proteins presented on MHC class II molecules efficiently stimulate antigen specific B cells. Although MHC class II molecules have been thought to present peptide antigens to T cells, our findings indicate that MHC class II molecules can present protein antigens to B cells. Furthermore, when we analyzed autoantibodies from autoimmune patients, we found that proteins presented on MHC class II molecules are specifically recognized by autoantibodies. These findings suggested that misfolded proteins aberrantly presented on MHC class II molecules are a target autoimmune diseases.