Structure Function Analysis of T Cell E-Selectin Ligands

描述（由申请方提供）：通过粘附事件的逐步级联，从血液中招募白细胞进入皮肤炎症部位。T细胞运输到皮肤炎症部位与皮肤淋巴细胞抗原（CLA）的表达密切相关，CLA是一种碳水化合物表位，其充当T细胞上的E-选择素配体并介导T细胞募集中的第一个关键步骤。CLA以前已经显示在称为P-选择素糖蛋白配体-1（PSGL-1）的白细胞唾液粘蛋白上差异表达。我们最近发现，CD 43，一种与PSGL-1结构相似的唾液粘蛋白，和一种未鉴定的100 kD唾液糖蛋白（gpl 00）也可以作为CLA+ T细胞上的E-选择素配体。这些以前未知的T细胞选择素配体被确定使用两种新的检测方法，我们已经开发。目前还没有关于CD 43上E-选择素配体决定簇或T细胞上100 kD糖蛋白的结构或调控的公开数据。这些以前未知的配体可能发挥重要的，目前尚未确定的作用，在免疫监视和招募白细胞的炎症部位。在本申请中，我们概述了实验，将表征T细胞上表达的单个E-选择素配体。在这些配体中识别共同的基序可以直接导致E-选择素介导的粘附的共同抑制剂的设计和开发，这可能在炎症性疾病如慢性自身免疫性疾病、移植物抗宿主病和移植排斥中具有重要价值。

DESCRIPTION (provided by applicant): Recruitment of leukocytes from blood into cutaneous inflammatory sites occurs via a stepwise cascade of adhesion events. T cell trafficking to sites of cutaneous inflammation has been closely associated with expression of the cutaneous lymphocyte antigen (CLA), a carbohydrate epitope that serves as an E-selectin ligand on T cells and mediates the first, crucial steps in T cell recruitment. CLA has been shown previously to be differentially expressed on a leukocyte sialomucin called P-selectin glycoprotein ligand-1 (PSGL-1). We have recently discovered that CD43, a sialomucin similar in structure to PSGL-1, and an unidentified 100kD sialoglycoprotein (gpl00) can also serve as E-selectin ligands on CLA+ T cells. These previously unknown T cell selectin ligands were identified using two novel assay methods we have developed. There is, at present, no published data regarding the structure or regulation of E-selectin ligand determinants on CD43 or a 100 kD glycoprotein on T cells. These previously unknown ligands may play important, currently undefined roles in immune surveillance and the recruitment of leukocytes to inflammatory loci. In this application, we outline experiments that will characterize the individual E-selectin ligands expressed on T cells. The identification of common motifs among these ligands could lead directly to the design and development of common inhibitors of E-selectin mediated adhesion that may be of significant value in inflammatory disorders such as chronic autoimmune disease, graft-versus-host disease and transplantation rejection.