The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1.
The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1.
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DOI：
10.1084/jem.174.6.1461
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发表时间：
1991-12-01
期刊：
影响因子：
--
通讯作者：
Butcher EC
中科院分区：
文献类型：
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作者：
Berg EL;Yoshino T;Rott LS;Robinson MK;Warnock RA;Kishimoto TK;Picker LJ;Butcher EC
与皮肤相关的记忆性 T 淋巴细胞群，由皮肤淋巴细胞抗原 (CLA) 的表达来定义，选择性地、强烈地与血管凝集素内皮细胞-白细胞粘附分子 1 (ELAM-1) 结合，这种相互作用可能涉及 CLA+ T 细胞靶向慢性炎症的皮肤部位。在这里，我们提供证据表明 CLA 本身是 ELAM-1 的（或 a）淋巴细胞归巢受体。用抗 CLA 单克隆抗体 HECA-452 从人扁桃体裂解物中分离出的抗原与 ELAM-1 转染的小鼠细胞密切结合。抗 CLA 抗体可阻断 T 淋巴细胞与 ELAM-1 转染子的结合。 HECA-452 和 ELAM-1 与淋巴细胞或分离的扁桃体 HECA-452 抗原的结合被神经氨酸酶治疗消除，这意味着唾液酸在 CLA 结构和功能中发挥着重要作用。 T 细胞上 CLA 的主要形式在免疫学上与主要中性粒细胞 ELAM-1 配体、唾液酸 Lewis x (sLex) 抗原 (NeuAc α 2-3Gal beta 1-4[Fuc α 1-3]GlcNAc) 不同，后者在 T 细胞上不存在、表达较弱或被屏蔽。然而，神经氨酸酶处理 CLA+ T 细胞而非 CLA- T 细胞，揭示了 Lewis x (CD15) 结构。结合 ELAM-1 和 HECA-452 结合所需的末端 NeuAc α 2-3Gal 和岩藻糖残基与 N-乙酰氨基葡萄糖连接的已知要求，这一发现表明 CLA 可能包含另外的唾液酸化或其他修饰形式的 sLex。皮肤淋巴细胞归巢受体的鉴定可能会为皮肤和炎症性疾病的诊断和治疗提供新的方法。
A skin-associated population of memory T lymphocytes, defined by expression of the cutaneous lymphocyte antigen (CLA), binds selectively and avidly to the vascular lectin endothelial cell-leukocyte adhesion molecule 1 (ELAM-1), an interaction that may be involved in targeting of CLA+ T cells to cutaneous sites of chronic inflammation. Here we present evidence that CLA itself is the (or a) lymphocyte homing receptor for ELAM-1. Antigen isolated with anti-CLA monoclonal antibody HECA-452 from human tonsillar lysates avidly binds ELAM-1 transfected mouse cells. Anti-CLA antibody blocks T lymphocyte binding to ELAM-1 transfectants. HECA-452 and ELAM-1 binding to lymphocytes or to isolated tonsillar HECA-452 antigen is abrogated by neuraminidase treatment implying a prominent role for sialic acid in CLA structure and function. The dominant form of CLA on T cells is immunologically distinct from the major neutrophil ELAM-1 ligand, the sialyl Lewis x (sLex) antigen (NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc), which is absent, weakly expressed, or masked on T cells. However, neuraminidase treatment of CLA+ T cells, but not of CLA- T cells, reveals Lewis x (CD15) structures. In combination with the known requirement for terminal NeuAc alpha 2-3Gal and fucose residues attached to N-acetylglucosamine for ELAM-1 and HECA-452 binding, this finding suggests that CLA may comprise an additionally sialylated or otherwise modified form of sLex. The identification of a lymphocyte homing receptor for skin may permit novel approaches to the diagnosis and therapy of cutaneous and inflammatory disorders.