Structure Function Analysis of T Cell E-Selectin Ligands

白细胞从血液中募集到皮肤炎症部位是通过一个逐步级联反应发生的。 粘连事件T细胞向皮肤炎症部位的运输与 表达皮肤淋巴细胞抗原（CLA），一种作为E-选择素的碳水化合物表位 它是T细胞上的配体，并介导T细胞募集的第一个关键步骤。CLA以前曾被证明 差异表达的白细胞唾液粘蛋白称为P-选择素糖蛋白配体-1（PSGL-1）。 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唾液酸糖蛋白（gpl 00）也可以作为CLA+ T细胞上的E-选择素配体。这些先前 未知的T细胞选择素配体用我们开发的两种新的测定方法鉴定。是的， 目前，还没有关于CD 43上E-选择素配体决定簇的结构或调控的公开数据 或T细胞上的100 kD糖蛋白。这些以前未知的配体可能发挥重要作用， 在免疫监视和白细胞向炎性位点募集中的作用不明确。在这 建议，我们概述了实验，将表征个人E-选择素配体T细胞上表达。 在这些配体中识别共同的基序可以直接导致设计和开发 E-选择素介导的粘附的常见抑制剂，可能在炎症中具有重要价值， 疾病如慢性自身免疫性疾病、移植物抗宿主病和移植排斥。

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 100 kD 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 proposal, 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.