Limited clonality in autoimmunity: drivers and regulators.
Limited clonality in autoimmunity: drivers and regulators.
复制标题
自身免疫的有限克隆性：驱动因素和调节因素。
DOI：
10.1016/j.autrev.2004.07.008
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sercarz,EliE
中科院分区：
文献类型：
--
作者：
vandenElzen,Peter;Menezes,JuscileneS;Ametani,Akio;Maverakis,Emanual;Madakamutil,Loui;Tang,Xiao-lei;Kumar,Vipin;Sercarz,EliE
针对自身的可用T细胞库是可观的，这是由于许多克隆从阴性选择中逃脱，主要是因为自身蛋白上的许多决定簇是隐蔽的并且没有充分呈现。此外，T细胞受体特异性的简并性允许每个淋巴细胞具有广泛的增殖潜力。在可用的自身反应库中，有高亲和力的T细胞，这些细胞可以与具有相同特异性的其他T细胞有利地竞争。我们研究了一个“驱动克隆”和它的两个特定的监管机构在B10.PL模型的实验性自身免疫性脑脊髓炎，发现这些剧目是高度有限的。有一个单一的主要克隆家族，包括侵略性的驱动程序人口，这是公共和高亲和力，只有一个其他次要的公共克隆型。这种Vβ8.2/Jβ2.7驱动因子的受体被呈递给CD 4调节因子和CD 8抑制因子，每一个都具有有限的克隆性，后者通过细胞凋亡杀死驱动因子克隆，完成反馈控制回路。这种由三种细胞类型组成的受到严格调控的群体是免疫侏儒的一个很好的例子。
The available T cell repertoire directed against self is appreciable owing to the escape of many clones from negative selection, largely because many determinants on self proteins are cryptic and not presented adequately. In addition, the degeneracy of T cell receptor specificity permits each lymphocyte a broad recognitive potential. Within the available self-reactive repertoire are T cells with high affinity, and these can compete favorably with other T cells with the same specificity. We have studied a “driver clone” and its two specific regulators in the B10.PL model of experimental autoimmune encephalomyelitis and found that each of these repertoires is highly limited. There is a single major clonal family comprising the aggressive driver population, which is public and of high affinity, and just one other minor public clonotype. The receptors of this Vβ8.2/Jβ2.7 driver are presented to a CD4 regulator and a CD8 suppressor, each of limited clonality, the latter killing the driver clone by apoptosis, completing a feedback control loop. This tightly regulated group of three cell types furnishes an excellent example of the immune homunculus.