MHC-independent T cells

胸腺产生MHC限制性abT细胞，仅识别与MHC或MHC样分子相关的抗原配体。我们假设CD4和CD8辅助受体可能在胸腺选择过程中对更广泛的abTCR库施加mhc特异性，因为它们结合并有效地隔离酪氨酸激酶Lck，从而阻止不参与任何辅助受体的非mhc配体的TCR信号传导。利用CD4和CD8以及MHC缺陷的小鼠，我们发现在体内缺乏协受体的情况下，ab胸腺细胞可以通过非MHC配体进行信号传导。此外，我们通过将CD4转基因引入quad缺陷小鼠，测试了辅助受体的关键作用。然而，野生型CD4对Lck的隔离阻断了ab胸腺细胞上非mhc配体的信号传导，引入了无尾形式的CD4细胞。我们得出结论，在缺乏Lck隔离的情况下，胸腺细胞可以通过非mhc配体进行信号传导。因此，CD4和CD8通过阻止胸腺细胞被非mhc配体选择，对广泛的abTCR库施加mhc特异性。

The thymus produces MHC-restricted abT cells that only recognize antigenic ligands in association with MHC or MHC-like molecules. We hypothesized that CD4 and CD8 coreceptors might be impose MHC-specificity on a broader abTCR repertoire during thymic selection because they bind and effectively sequester the tyrosine kinase Lck, thereby preventing TCR signaling by non-MHC ligands that do not engage either coreceptor. Using mice deficient for both CD4 and CD8 as well as MHC (Quad-deficient), we discoverd that ab thymocytes can be signaled by non-MHC ligands in the absence of coreceptors in vivo. In addition, we tested the critical role of coreceptors by introducing CD4 transgenes into Quad-deficient mice. Whereas sequestration of Lck by wild-type CD4 blocked signaling by non-MHC ligands on ab thymocytes, introducing a tailless form of CD4 didnt. We conclude that in the absence of Lck sequestration by coreceptors, thymocytes can be signaled by non-MHC ligands. Therefore, CD4 and CD8 impose MHC-specificity on a broad abTCR repertoire by preventing thymocytes to be selected by non-MHC ligands.