Separation of thymic education from antigen presenting functions of major histocompatibility complex class I molecules.
Separation of thymic education from antigen presenting functions of major histocompatibility complex class I molecules.
复制标题
将胸腺教育与主要组织相容性复合物 I 类分子的抗原呈递功能分开。
作者：
E. Simpson;P. Robinson;P. Chandler;M. Millrain;H. Pircher;D. Brändle;P. Tomlinson;J. Antoniou;A. Mellor
利用转基因小鼠研究了跨膜蛋白(TM)和糖基磷脂酰肌醇(GPI)锚定的H-2DB分子在抗原提呈和胸腺选择活动中的作用。GPI-DB和TM-DB都能有效地将H-Y抗原、流感病毒和淋巴细胞性脉络膜脑膜炎病毒(LCMV)多肽递送到H-2DB限制性的细胞毒性T细胞。表达GPI-DB的转基因小鼠虽然不能排斥TM-DB皮肤移植，但仍能产生二次CTL反应，能够溶解TM-DB携带的靶细胞，这表明GPI-DB小鼠不能删除所有TM-DB反应性T细胞。此外，携带GPI-DB和H-2DB+LCMV的T细胞受体(TCR)的双转基因小鼠不能积极选择受体阳性的CD8+CD4-T细胞。GPI-DB分子的这种矛盾行为表明，I类分子对抗原提呈和胸腺选择的结构要求是不同的，这可能解释了为什么GPI连接的I类分子，如Qa-2，在体内似乎不起限制元件的作用。
Participation of transmembrane (TM) and glycosyl-phosphatidylinositol (GPI) anchored H-2Db molecules in antigen presentation and thymic selection events was investigated using transgenic mice. Both GPI-Db and TM-Db can efficiently present H-Y antigen, influenza and lymphocytic choriomeningitis virus (LCMV) peptides to primed cytotoxic, H-2Db-restricted T cells. Transgenic mice expressing GPI-Db, although unable to reject TM-Db skin grafts, nevertheless generate secondary CTL responses which can lyse TM-Db-bearing targets, indicating that GPI-Db mice fail to delete all TM-Db-reactive T cells. Furthermore, double-transgenic mice bearing GPI-Db and a T-cell receptor (TcR) for H-2Db+LCMV do not positively select receptor positive, CD8+CD4- T cells. This paradoxical behaviour of GPI-Db molecules suggests that the structural requirements for antigen presentation and thymic selection by class I molecules are different and may explain why GPI-linked class I molecules, such as Qa-2, do not appear to function as restriction elements in vivo.