Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ.
Distinct temporal patterns of T cell receptor signaling during positive versus negative selection in situ.
复制标题
T细胞受体信号传导的不同时间模式在正选择与负面选择过程中。
DOI：
10.1126/scisignal.2004400
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发表时间：
2013-10-15
影响因子：
7.3
通讯作者：
Robey EA
中科院分区：
文献类型：
--
作者：
Melichar HJ;Ross JO;Herzmark P;Hogquist KA;Robey EA
T细胞受体（TCR）对主要组织相容性复合体（MHC）呈递的自身肽的识别控制胸腺中的T细胞命运，弱信号诱导存活（正选择过程），强信号诱导死亡（负选择）。体外研究表明，产生阳性选择的配体诱导低但持续的TCR信号传导模式;然而，在支持阳性选择的条件下，在胸腺中由MHC I类（MHC I类限制）呈递肽的胸腺细胞中TCR信号传导的时间模式尚不清楚。在这里，我们解决了这个问题，通过检查细胞内钙（Ca 2+）动力学和迁移的变化，在胸腺切片中进行积极和消极的选择胸腺细胞。我们发现，短暂的，串行信号事件，迁移期间和低胞质Ca 2+分离与MHC I类限制性胸腺细胞的阳性选择，而持续的信号和胸腺细胞的逮捕与阴性选择。低亲合力肽和皮质胸腺上皮细胞的肽呈递未能诱导胸腺细胞的强烈迁移停滞，这导致瞬时TCR信号传导。因此，我们提供了一个比较的积极和消极的选择信号在原位，并建议强烈的停止信号的情况下是一个重要的功能，区分积极和消极的选择。
The recognition by the T cell receptor (TCR) of self peptides presented by the major histocompatibility complex (MHC) controls T cell fate in the thymus, with weak signals inducing survival (the process of positive selection) and stronger signals inducing death (negative selection). In vitro studies have indicated that ligands that give rise to positive selection induce a low, but sustained, pattern of TCR signaling; however, the temporal pattern of TCR signaling in thymocytes that are presented peptide by MHC class I (MHC class I restriction) in they thymus, under conditions that support positive selection, are unknown. Here, we addressed this question by examining intracellular calcium (Ca2+) dynamics and migratory changes in thymocytes undergoing positive and negative selection in thymic slices. We found that brief, serial signaling events that were separated by migratory periods and low cytosolic Ca2+ correlated with the positive selection of MHC class I–restricted thymocytes, whereas sustained signaling and arrest of thymocytes were associated with negative selection. Low avidity peptides and the presentation of peptides by cortical thymic epithelial cells failed to induce strong migratory arrest of thymocytes, which led to transient TCR signaling. Thus, we provide a comparison of positive and negative selection signals in situ and suggest that the absence of strong stop signals is an important feature that distinguishes between positive and negative selection.
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影响因子：
15.9
作者：
Halkias, Joanna;Melichar, Heather J.;Robey, Ellen A.
通讯作者：
Robey, Ellen A.
影响因子：
32.4
作者：
Ehrlich, Lauren I. Richie;Oh, David Y.;Lewis, Richard S.
通讯作者：
Lewis, Richard S.
影响因子：
64.8
作者：
Daniels, Mark A.;Teixeiro, Emma;Palmer, Ed
通讯作者：
Palmer, Ed
影响因子：
30.5
作者：
Bhakta, NR;Oh, DY;Lewis, RS
通讯作者：
Lewis, RS
影响因子：
4.4
作者：
Ladi, Ena;Schwickert, Tanja A.;Robey, Ellen A.
通讯作者：
Robey, Ellen A.