SELECTIVE DEVELOPMENT OF CD4+ T-CELLS IN TRANSGENIC MICE EXPRESSING A CLASS-II MHC-RESTRICTED ANTIGEN RECEPTOR
SELECTIVE DEVELOPMENT OF CD4+ T-CELLS IN TRANSGENIC MICE EXPRESSING A CLASS-II MHC-RESTRICTED ANTIGEN RECEPTOR
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DOI：
10.1038/341746a0
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发表时间：
1989-10-26
期刊：
影响因子：
64.8
通讯作者：
HEDRICK, SM
中科院分区：
文献类型：
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作者：
KAYE, J;HSU, ML;HEDRICK, SM
T淋巴细胞倾向于识别与主要组织相容性复合体（MHC）编码的细胞表面分子结合的外源蛋白片段1，2。现在有令人信服的证据表明，这种特异性是一个选择过程的结果，在胸腺中发育的T淋巴细胞3 -6。由于这种阳性选择，表达对自身MHC编码的糖蛋白具有阈值亲和力的抗原受体的胸腺细胞优先从胸腺和种子外周淋巴器官中迁移。对外源抗原和MHC分子的特异性由T细胞抗原受体（TCR）的α和β链赋予7，8。另外两种T细胞表面蛋白，CD 4和CD 8，分别结合II类和I类MHC分子的非多态性区域，也参与这些识别事件，并在胸腺选择中发挥不可或缺的作用。为了阐明II类MHC-静止的T细胞与这些必需的辅助分子的关系的发育途径，我们已经产生了TCR-转基因小鼠，其表达对鸽子细胞色素c和Ek（II类MHC）分子的片段具有特异性的受体。转基因TCR在表达k的小鼠中几乎所有T细胞上表达。这些小鼠的胸腺含有异常高比例的成熟CD 4 + CD 8 −细胞。此外，外周T细胞群几乎完全是CD 4+，表明TCR的MHC特异性决定了胸腺中选择期间T细胞的表型。
T LYMPHOCYTES are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC)1, 2. There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus3–6. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by theαandβchains of the T-cell antigen receptor (TCR)7, 8. Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively9, 10, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-rest rioted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek(class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressingk. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8−cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.