ENHANCEMENT OF T-CELL ACTIVATION BY THE CD43 MOLECULE WHOSE EXPRESSION IS DEFECTIVE IN WISKOTT-ALDRICH SYNDROME
ENHANCEMENT OF T-CELL ACTIVATION BY THE CD43 MOLECULE WHOSE EXPRESSION IS DEFECTIVE IN WISKOTT-ALDRICH SYNDROME
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DOI：
10.1038/350706a0
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发表时间：
1991-04-25
期刊：
影响因子：
64.8
通讯作者：
BURAKOFF, SJ
中科院分区：
文献类型：
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作者：
PARK, JK;ROSENSTEIN, YJ;BURAKOFF, SJ
CD 43（唾液酸蛋白、白细胞唾液酸蛋白、白细胞大唾液酸糖蛋白）是在大多数白细胞和血小板上发现的重度唾液酸化分子，最初被鉴定为小鼠、大鼠和人T细胞的主要糖蛋白1-8。 Wiskott-Aldrich综合征（一种X染色体连锁隐性免疫缺陷疾病）男性T细胞上的CD 43表达存在缺陷9。 受影响的男性容易受到机会性感染，对多糖抗原没有反应，反映了细胞毒性和辅助性T细胞功能的缺陷。 抗CD 43单克隆抗体对T细胞、自然杀伤细胞、B细胞和单核细胞具有适度的共刺激作用10-14，并且已经显示一种这样的抗体直接激活T细胞15。 为了研究CD 43可能的生理作用，将编码人蛋白质16、17的互补DNA引入抗原应答性鼠T细胞杂交瘤18中。 我们观察到CD 43增强T细胞的抗原特异性活化，并且在T细胞活化期间过度磷酸化的CD 43的胞内结构域19-21是该功能所需的。 我们还发现，抗原呈递细胞可以特异性地结合到固定的纯化的CD 43，并且该结合可以被含有CD 43的脂质体以及抗CD 43单克隆抗体抑制。
CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells 1-8. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder 9. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes 10-14, and one such antibody has been shown to activate T cells directly 15. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein 16,17 was introduced into an antigen-responsive murine T-cell hybridoma 18. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation 19-21, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies.