Identification of Islet Proteins Stimulatory to T Cells from Autoimmune Diabetic

描述（由申请人提供）：糖尿病主要由两种临床上独立的疾病组成：1型和2型糖尿病。1型糖尿病是一种针对β细胞的细胞介导的自身免疫性疾病，其特征在于自身抗体和T细胞对胰岛蛋白的反应性。相反，2型糖尿病不是自身免疫性的，而是由胰岛素抵抗和非自身免疫性胰岛素分泌缺陷引起的。然而，存在表型2型糖尿病患者的亚组，其具有对1型患者特征性胰岛细胞蛋白的自身抗体和T细胞应答。已经使用了几个名称来描述这些患者，包括成人隐匿性自身免疫性糖尿病（LADA），缓慢进展的1型和1.5型糖尿病。已经在1型和成人1.5型糖尿病患者之间确定了对胰岛蛋白的免疫反应性的差异。我们观察到1型与成人1.5型糖尿病患者的T细胞识别的特异性胰岛蛋白、识别的胰岛蛋白数量和胰岛细胞识别的幅度存在明显差异。这项研究的重点是从1型糖尿病患者和沿着成人1.5型糖尿病患者中鉴定刺激T细胞的胰岛蛋白，以及可能区分这两种形式的自身免疫性糖尿病的胰岛蛋白。刺激性胰岛蛋白的鉴定将允许这些蛋白用于诊断以及具有用于监测免疫调节疗法的临床应用。

DESCRIPTION (provided by applicant): Diabetes is comprised primarily of two clinically separate diseases: type 1 and type 2 diabetes. Type 1 diabetes is a cell-mediated autoimmune disease directed against the beta-cells and characterized by autoantibody and T cell reactivity to islet proteins. In contrast, type 2 diabetes is not autoimmune, but rather results from both insulin resistance, and a non-autoimmune insulin secretory defect. However, there is a subgroup of phenotypic type 2 diabetes patients who have autoantibodies and T cell responses to islet cell proteins characteristic of type 1 patients. Several names have been used to describe these patients including latent autoimmune diabetes in adults (LADA), slowly progressive type 1, and type 1.5 diabetes. Differences in immune reactivity to islet proteins have been identified between type 1 and adult type 1.5 diabetes patients. We observed apparent differences in specific islet proteins recognized, the number of islet proteins recognized, and the magnitude of islet cell recognition by T cells from type 1 versus adult type 1.5 diabetes patients. Studies in this grant will focus on identification of islet proteins stimulatory to T cells from both type 1 diabetes patients and adult type 1.5 diabetes patients along with islet proteins that may distinguish these two forms of autoimmune diabetes. Identification of the stimulatory islet proteins will allow for these proteins to be used for diagnostic as well as have clinical applications for monitoring immunomodulatory therapies.