Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells
Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells
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DOI：
10.1038/40166
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发表时间：
1997-10-30
期刊：
影响因子：
64.8
通讯作者：
Kupper, TS
中科院分区：
文献类型：
--
作者：
Fuhlbrigge, RC;Kieffer, JD;Kupper, TS
T细胞在许多炎症性和某些恶性皮肤病中起致病作用，包括牛皮癣、特应性和过敏性接触性皮炎和皮肤T细胞淋巴瘤（1-6）。浸润皮肤的记忆T细胞表达一种独特的皮肤归巢受体，称为皮肤淋巴细胞相关抗原（CLA），这是一种碳水化合物表位，可促进T细胞靶向炎症皮肤（1,7,8）。CLA的定义是它与一种独特的单克隆抗体HECA-452的反应性，以及它作为e -选择素配体的活性（2,9-11），但CLA的蛋白质成分的结构以前没有被定义。本文报道CLA是p -选择素糖蛋白配体1 （PSGL-1）的可诱导碳水化合物修饰，PSGL-1是一种已知的表面糖蛋白，在所有人外周血T细胞上组成性表达，培养的外周血T细胞可以分化为携带CLA的细胞，其结合e -选择素和p -选择素，或CLA阴性细胞，其结合p -选择素但不结合e -选择素，这表明存在独立的选择素结合表型调控。我们提出，由focusyltransferase VII介导的单个细胞表面受体PSGL-1的翻译后差异修饰可作为调节记忆T细胞组织特异性归巢的机制。
T cells play a pathogenic role in many inflammatory and certain malignant skin diseases, including psoriasis, atopic and allergic contact dermatitis, and cutaneous T-cell lymphoma(1-6). Memory T cells that infiltrate the skin express a unique skin-homing receptor called cutaneous lymphocyte-associated antigen (CLA), a carbohydrate epitope that facilitates the targeting of T cells to inflamed skin(1,7,8). CLA is defined by both its reactivity with a unique monoclonal antibody, HECA-452, and its activity as a ligand for E-selectin(2,9-11), but the structure of the protein component of CLA has not previously been defined. Here we report that CLA is an inducible carbohydrate modification of P-selectin glycoprotein ligand-1 (PSGL-1), a known surface glycoprotein that is expressed constitutively on all human peripheral-blood T cells, Cultured peripheral-blood T cells can be differentiated into CLA-bearing cells, which bind both E-selectin and P-selectin, or CLA-negative cells, which bind P-selectin but do not bind E-selectin, suggesting that there is independent regulation of selectin-binding phenotypes, We propose that differential post-translational modification of a single cell-surface receptor, PSGL-1, mediated by fucosyltransferase VII, serves as a mechanism for regulating tissue-specific homing of memory T cells.