Roep B O, Arden S D, de Vries R R, Hutton J C
Department of Immunohaematology and Blood Bank, University Hospital, Leiden, The Netherlands.
Nature. 1990 Jun 14;345(6276):632-4. doi: 10.1038/345632a0.
T LYMPHOCYTES reactive to pancreatic beta-cells are thought to have a central role in the autoimmune process leading to type 1 (insulin-dependent) diabetes, but the molecular targets of these T cells have not yet been defined. As identification of such antigens may enable measures to be developed to prevent the disease, we have characterized an antigen that is recognized by insulinoma membrane-reactive T-cell clones established from a newly diagnosed type-1 diabetes patient. Subcellular fractionation studies using rat insulinoma indicate that the antigenic determinant recognized by one of these clones is an integral membrane component of the insulin secretory granule. After a 5,000-fold purification, we have defined the antigen as a monomer of relative molecular mass 38,000. As granular membrane proteins are transiently exposed on the cell surface during exocytosis, their accessibility to components of the immune system may be a function of the secretory activity of beta-cells.
对胰腺β细胞有反应的T淋巴细胞被认为在导致1型（胰岛素依赖型）糖尿病的自身免疫过程中起核心作用，但这些T细胞的分子靶点尚未明确。由于鉴定此类抗原可能有助于开发预防该疾病的措施，我们已对一种抗原进行了特性分析，该抗原可被从一名新诊断的1型糖尿病患者身上建立的胰岛素瘤膜反应性T细胞克隆所识别。使用大鼠胰岛素瘤进行的亚细胞分级分离研究表明，这些克隆之一所识别的抗原决定簇是胰岛素分泌颗粒的一种整合膜成分。经过5000倍的纯化后，我们将该抗原定义为相对分子质量为38000的单体。由于颗粒膜蛋白在胞吐过程中会短暂暴露于细胞表面，它们对免疫系统成分的可及性可能是β细胞分泌活性的一种功能。
