CD8+ T cell activation is governed by TCR-Peptide/MHC affinity, not dissociation rate
CD8+ T cell activation is governed by TCR-Peptide/MHC affinity, not dissociation rate
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DOI：
10.4049/jimmunol.179.5.2952
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Frelinger, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Tian, Shaomin;Maile, Robert;Frelinger, Jeffrey A.
TCR与肽/MHC（pMHC）复合物的结合启动T细胞活化。尽管长期的兴趣，TCR/pMHC相互作用的生物化学（特别是TCR亲和力或配体解离速率）和T细胞反应之间的确切关系仍然没有得到解决，因为在每个独立的系统中检测的复合物的数量太少，无法得出明确的结论。为了测试当前的T细胞活化模型，我们分析了小鼠P14 TCR和一组基于与小鼠I类MHC D-b结合的淋巴细胞性脉络丛脑膜炎病毒表位gp 33 -41序列的改变的肽之间的相互作用。测量肽的pMHC结合、TCR结合特征、CD 8（+）T细胞毒性和IFN-γ产生。我们发现亲和力与细胞毒性和IFN-γ的产生密切相关。相反，在TCR-pMHC相互作用的任何动力学参数与细胞毒性或IFN-γ产生之间未观察到相关性。这项研究有力地论证了T细胞活化的亲和力阈值模型。
Binding of peptide/MHC (pMHC) complexes by TCR initiates T cell activation. Despite long interest, the exact relationship between the biochemistry of TCR/pMHC interaction (particularly TCR affinity or ligand off-rate) and T cell responses remains unresolved, because the number of complexes examined in each independent system has been too small to draw a definitive conclusion. To test the current models of T cell activation, we have analyzed the interactions between the mouse P14 TCR and a set of altered peptides based on the lymphocytic choriomeningitis virus epitope gp33-41 sequence bound to mouse class I MHC D-b. pMHC binding, TCR-binding characteristics, CD8(+) T cell cytotoxicity, and IFN-gamma production were measured for the peptides. We found affinity correlated well with both cytotoxicity and IFN-gamma production. In contrast, no correlation was observed between any kinetic parameter of TCR-pMHC interaction and cytotoxicity or IFN-gamma production. This study strongly argues for an affinity threshold model of T cell activation.