T-cell-receptor affinity and thymocyte positive selection
T-cell-receptor affinity and thymocyte positive selection
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DOI：
10.1038/381616a0
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发表时间：
1996-06-13
期刊：
影响因子：
64.8
通讯作者：
Gascoigne, NRJ
中科院分区：
文献类型：
--
作者：
Alam, SM;Travers, PJ;Gascoigne, NRJ
胸腺细胞的发育涉及两种由表面相似事件导致的截然不同的结果。胸腺细胞对主要组织相容性复合体（MHC）蛋白加上肽的识别使其免于凋亡（阳性选择），而对抗原肽的识别则诱导细胞死亡（阴性选择）（1）。抗原类似物（1 - 3），有时还有低浓度的抗原肽（4，5），诱导阳性选择；这类类似物通常是成熟T细胞克隆的拮抗剂（1 - 3，6）。多种模型试图解释对不同肽/MHC复合物的识别如何导致如此不同的结果（1，7 - 10）：定量模型将反应与T细胞 - 抗原受体（TCR）结合的亲和力、亲合力或动力学相关联，而定性模型则要求TCR或相关分子发生构象或空间变化以调节信号转导（7，9）。我们利用表面等离子体共振（11）来测量TCR与阳性和阴性选择配体相互作用的动力学，以区分这些模型，并发现亲和力与选择的结果相关。导致阳性选择的亲和力“窗口”在比阴性选择亲和力低三倍开始的1个对数范围内延伸。
DEVELOPMENT Of thymocytes involves two distinct outcomes resulting from superficially similar events, Recognition by thymocytes of major histocompatibility complex (MHC) proteins plus peptide leads to their rescue from apoptosis (positive selection), and recognition of antigenic peptide induces cell death (negative selection)(1), Antigen analogues(1-3), and sometimes low concentrations of antigenic peptide(4,5), induce positive selection; such analogues are often antagonists of mature T-cell clones(1-3,6) Various models seek to explain how recognition of different peptide/MHC complexes leads to such different outcomes(1,7-10): quantitative models relate response to the affinity, avidity or kinetics of T cell-antigen receptor (TCR) binding, whereas qualitative models require conformational or spatial changes in the TCR or associated molecules to modulate signal transduction(7,9). We have used surface plasmon resonance(11) to measure the kinetics of TCR interactions with positively and negatively selecting ligands to distinguish between these models, and find that affinity correlates to the outcome of selection. A 'window' of affinity resulting in positive selection extends over a 1-log range starting threefold below the affinity for negative selection.