Activation of the TCR complex by peptide-MHC and superantigens.
Activation of the TCR complex by peptide-MHC and superantigens.
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DOI：
10.1007/978-3-0348-0726-5_2
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发表时间：
2014
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影响因子：
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通讯作者：
C. Louis-dit-Sully;B. Blumenthal;M. Duchniewicz;Katharina Beck-García;Gina J. Fiala;Esmeralda Beck-García;Markus Mukenhirn;S. Minguet;W. Schamel
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文献类型：
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作者：
C. Louis-dit-Sully;B. Blumenthal;M. Duchniewicz;Katharina Beck-García;Gina J. Fiala;Esmeralda Beck-García;Markus Mukenhirn;S. Minguet;W. Schamel
药物超敏反应是免疫介导的，药物通过其T细胞抗原受体（TCR）刺激T淋巴细胞。在非致病状态下，TCR被主要组织相容性复合物分子（pMHC）呈递的外源肽激活。外源pMHC以足够的亲和力与TCRαβ结合，从而增强TCRαβ相关CD 3亚基的胞质尾的磷酸化。这个过程被称为TCR触发。在这篇综述中，我们讨论了目前的TCR触发模型和药物的性质是至关重要的TCR刺激。潜在的分子机制主要包括pMHC诱导的CD 3胞质尾区暴露或CD 3附近激酶-磷酸酶平衡的改变。在这篇综述中，我们还讨论了触发TCR的小化学化合物的背景下，这些一般机制。
Drug hypersensitivity reactions are immune mediated, with T lymphocytes being stimulated by the drugs via their T-cell antigen receptor (TCR). In the nonpathogenic state, the TCR is activated by foreign peptides presented by major histocompatibility complex molecules (pMHC). Foreign pMHC binds with sufficient affinity to TCRαβ and thereby elicits phosphorylation of the cytoplasmic tails of the TCRαβ-associated CD3 subunits. The process is called TCR triggering. In this review, we discuss the current models of TCR triggering and which drug properties are crucial for TCR stimulation. The underlying molecular mechanisms mostly include pMHC-induced exposure of the CD3 cytoplasmic tails or alterations of the kinase-phosphatase equilibrium in the vicinity of CD3. In this review, we also discuss triggering of the TCR by small chemical compounds in context of these general mechanisms.