A NOVEL FAMILY OF LYMPHOCYTE ADHESION MOLECULES

描述：T细胞活化是由一个高度组织化的 在T细胞-抗原呈递细胞界面处的多分子结构。这 这种结构最近被称为“免疫突触”。“为了努力 他们发现了参与这种突触的新分子，他们已经确定了一个家族， 五种以前未克隆的钙粘蛋白样淋巴细胞跨膜蛋白（ CLASP家族）。家族中至少有一个成员，鼠CLASP-I， 在免疫突触上。该研究项目第一阶段的目标是 克隆和测序该家族的至少三个人类基因， 确定其组织表达模式和染色体定位。在 此外，干扰CLASP功能的分子，如单克隆 抗体或重组可溶性CLASP蛋白，将被合成，并且其 体外试验对淋巴细胞活化的影响。在项目的第二阶段， 这些潜在治疗剂的毒性和功效将在 器官移植和自身免疫性疾病的动物模型，如果阳性 在人体临床试验中获得了结果。这些研究 应该进一步加深他们对免疫突触的分子理解， 产生商业上可行的产品，通过靶向这种突触， 改善免疫系统的药理学调节。 拟议商业应用：不可用

DESCRIPTION: T cell activation is controlled by a highly organized multi-molecular structure at the T cell-antigen presenting cell interface. This structure has recently been termed an "immunological synapse." In an effort to find novel molecules involved in this synapse, they have identified a family of five previously uncloned cadherin-like lymphocyte transmembrane proteins (the CLASP family). At least one member of the family, murine CLASP-I, is localized at the immunological synapse. The goals of phase I of this research project are to clone and sequence at least three human genes of this family and to determine their tissue expression patterns and chromosomal localization. In addition, molecules that interfere with CLASP function, such as monoclonal antibodies or recombinant soluble CLASP proteins, will be synthesized and their effect on lymphocyte activation tested in vitro. In stage II of the project, the toxicity and efficacy of these potential therapeutics will be evaluated in animal models of organ transplantation and autoimmune disease and if positive results are obtained in clinical trials in humans. Together these studies should further their molecular understanding of the immunological synapse and yield commercially viable products that, by targeting this synapse, allow improved pharmacological regulation of the immune system. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE