Arsov I, Vukmanović S
Michael Heidelberger Division of Immunology, Department of Pathology, Kaplan Cancer Center, New York University Medical Center 10016, USA.
J Immunol. 1999 Feb 15;162(4):2008-15.
In the final stages of thymic development, immature T cells undergo three distinct processes (positive selection, negative selection, and lineage commitment) that all depend on interactions of thymocyte TCRs with MHC molecules. It is currently thought that TCRs are preferentially restricted by either MHC class I or class II molecules. In this report, we present direct evidence that the TCR previously described as H-Y/H-2Db specific cross-reacts with H-2IAb if expressed in CD4+ cells. We also demonstrate an increase in thymocyte numbers in H-Y TCR-trangenic mice deficient in MHC class II, suggesting a relatively discrete form of negative selection by MHC class II compared with that induced by H-Y/H-2Db. We propose that inability to generate CD4+ T cells expressing H-Y TCR in different experimental settings may be due to tolerance to self-MHC class II. These results, therefore, support an intriguing possibility that tolerance to self may influence and/or interfere with the outcome of the lineage commitment.
在胸腺发育的最后阶段，未成熟的T细胞经历三个不同的过程（阳性选择、阴性选择和谱系定向），这些过程都依赖于胸腺细胞TCR与MHC分子的相互作用。目前认为，TCR优先受MHC I类或II类分子的限制。在本报告中，我们提供了直接证据，即先前描述为H-Y/H-2Db特异性的TCR如果在CD4+细胞中表达，则会与H-2IAb发生交叉反应。我们还证明，在缺乏MHC II类分子的H-Y TCR转基因小鼠中，胸腺细胞数量增加，这表明与H-Y/H-2Db诱导的阴性选择相比，MHC II类分子诱导的阴性选择形式相对离散。我们提出，在不同的实验环境中无法产生表达H-Y TCR的CD4+ T细胞可能是由于对自身MHC II类分子的耐受性。因此，这些结果支持了一种有趣的可能性，即对自身的耐受性可能会影响和/或干扰谱系定向的结果。
