67KD NON INTEGRIN LAMININ BINDING PROTEIN IN T LYMPHOCYTE MEDIATED SKIN DISEASE

T细胞与基底膜主要糖蛋白层粘连蛋白的相互作用 膜，是重要的淋巴细胞迁移在皮肤 炎症反应（1-4）。然而，淋巴细胞之间的相互作用 与层粘连蛋白的关系才刚刚开始被了解。所依据 我们发现67 kD层粘连蛋白结合蛋白 (p67 LBP）表达于活化的T细胞表面，但不表达于静息T细胞表面。 淋巴细胞我们最初通过差异表达鉴定了p67 LBP， 表达编码其多肽前体p37 LBPP的mRNA， 一对T细胞肿瘤系亚克隆，其代表表型 静息或活化T细胞的特征。随后，委员会决定， 使用抗p67 LBP单克隆抗体（mAb）MLuC 5（6），我们 证明p67 LBP在活化的记忆T细胞上表达， 不表达于幼稚细胞或静息细胞。本补助金旨在解决 T细胞对p67 LBP表达的需求， 表达p67 LBP的T淋巴细胞，以及p67 LBP在 T细胞迁移到皮肤中。这些研究的长期目标 目的是确定p67 LBP在皮肤T细胞归巢中的作用， 确定潜在的治疗靶点在治疗免疫- 介导的皮肤病。我们建议解决以下具体问题： 目的： 1.什么样的刺激能诱导正常T细胞表达p67 LBP？ 2.表达p67 LBP的T细胞亚群的表型是什么？ 关于T淋巴细胞已知的交通到皮肤？ 3.浸润皮肤炎症部位的T细胞是否表达 p67 LBP？

T cell interactions with laminin, the major glycoprotein of the basement membrane, are important in lymphocyte migration in the cutaneous inflammatory response (1-4). However, the interactions of lymphocytes with laminin are only beginning to be understood. Underlying the proposed studies is our finding that the 67 kD laminin binding protein (p67 LBP) is expressed on the surface of activated but not resting T lymphocytes. We initially identified p67 LBP by the differential expression of the mRNA encoding its polypeptide precursor, p37 LBPP, in a pair of T cell tumor line subclones that represent phenotypic characteristics of either resting or activated T cells. Subsequently, suing the anti-p67 LBP monoclonal antibody (mAb) MLuC5(6), we demonstrated that p67 LBP is expressed on activated memory T cells, and not expressed on naive or resting cells. The present grant addresses the T cell requirements for p67 LBP expression, the nature of the subset of T lymphocytes which express p67 LBP, and the role that p67 LBP plays in T cell migration into the skin. The long term objective of these studies is to define the role of p67 LBP in cutaneous T cell homing, and to identify potential therapeutic targets in the treatment of immune- mediated skin disease. We propose to address the following specific aims: 1. What stimuli induce the expression of p67 LBP on normal T cell? 2. What is the phenotype of the p67 LBP-expressing T cell subset with respect to the T lymphocytes known to traffic to the skin? 3. Do the T cells infiltrating cutaneous sites of inflammation express p67 LBP?