An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a.
An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a.
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胸腺阳性选择是基于T细胞抗原受体（TCR）与自身肽-主要组织相容性复合物（MHC）配体的相互作用，但选择MHC II类限制性TCR的肽的身份和这种肽特异性的功能后果尚不清楚。在这里，我们确定了几个内源性自身肽，积极选择MHC II类限制性5C.C7 TCR。其中最有效的也增强了成熟T细胞的活化，这支持了正选择的一个功能是产生可以使用特定的自身肽-MHC复合物进行活化和/或稳态的T细胞的假设。我们还表明，抑制microRNA miR-181 a导致T细胞的成熟，这些T细胞对这些以前的阳性选择肽有明显的反应。因此，miR-181 a通过调节胸腺细胞的TCR信号传导阈值，有助于保证特定中等亲和力克隆的克隆缺失。
Thymic positive selection is based on the interactions of T cell antigen receptors (TCRs) with self peptide–major histocompatibility complex (MHC) ligands, but the identity of selecting peptides for MHC class II–restricted TCRs and the functional consequences of this peptide specificity are not clear. Here we identify several endogenous self peptides that positively selected the MHC class II–restricted 5C.C7 TCR. The most potent of these also enhanced mature T cell activation, which supports the hypothesis that one function of positive selection is to produce T cells that can use particular self peptide–MHC complexes for activation and/or homeostasis. We also show that inhibiting the microRNA miR-181a resulted in maturation of T cells that overtly reacted toward these erstwhile positively selecting peptides. Therefore, miR-181a helps to guarantee the clonal deletion of particular moderate-affinity clones by modulating the TCR signaling threshold of thymocytes.
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影响因子：
15.3
作者：
Baldwin, K K;Reay, P A;Wu, L;Farr, A;Davis, M M
通讯作者：
Davis, M M
DOI：
10.1084/jem.177.5.1469
发表时间：
1993-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hogquist KA;Gavin MA;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
32.4
作者：
Jones, Mary Elizabeth;Zhuang, Yuan
通讯作者：
Zhuang, Yuan
影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM