Early biochemical signals arise from low affinity TCR-ligand reactions at the cell-cell interface.
Early biochemical signals arise from low affinity TCR-ligand reactions at the cell-cell interface.
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DOI：
10.1084/jem.184.2.777
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发表时间：
1996-08-01
期刊：
影响因子：
--
通讯作者：
McConnell HM
中科院分区：
文献类型：
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作者：
Beeson C;Rabinowitz J;Tate K;Gütgemann I;Chien YH;Jones PP;Davis MM;McConnell HM
在短暂暴露于抗原肽期间，用微生理计测量 T 细胞和抗原呈递细胞的混合物释放酸的动力学。我们发现一些导致细胞增殖的早期生化事件会导致酸释放速率的特定增加。酸释放增加的持续时间反映了肽-MHC 复合物的寿命。形成长效复合物的肽可产生稳定超过一个小时的反应。观察到这种稳定反应的幅度可以通过额外的激动剂肽或阻断 T 细胞受体结合的抗体快速上移或下移，表明串行 TCR 参与。细胞短暂暴露于形成短寿命肽-MHC复合物的肽时，会产生一种反应，该反应随着肽被冲走而迅速衰减。对酸化过程中这种衰减动力学的定量分析表明，细胞间 TCR-配体反应是快速、可逆的，并且在任何时候与 TCR 结合的肽-MHC 配体的表观亲和力均低于 20%。这些结果表明，在细胞-细胞界面处与TCR结合的肽-MHC配体的分数不高于根据在溶液中观察到的分离的TCR和配体的亲和力所预期的。
The kinetics of acid release by a mixture of T cells and antigen presenting cells were measured with a microphysiometer during a brief exposure to antigenic peptides. We find that some of the early biochemical events that lead to cellular proliferation cause a specific increase in the rate of acid release. The duration of this increase in acid release reflects the life-time of the peptide-MHC complexes. Peptides that form long-lived complexes produce a response that is stable for more than an hour. Serial TCR engagement is suggested by the observation that the amplitude of this stable response can be rapidly shifted up or down with additional agonist peptide or with antibodies that block T cell receptor binding. Cells briefly exposed to a peptide that forms short-lived peptide-MHC complexes produce a response that decays rapidly as peptide is washed away. A quantitative analysis of the kinetics of this decay in acidification demonstrates that intercellular TCR-ligand reactions are rapid, reversible, and of low apparent affinity with < 20% of peptide-MHC ligand bound to a TCR at any one time. These results demonstrate that the fraction of peptide- MHC ligands bound to TCRs at the cell-cell interface is no higher than anticipated from the affinities observed in solution for isolated TCRs and ligands.
DOI：
10.1084/jem.159.3.704
发表时间：
1984-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Frelinger JG;Shigeta M;Infante AJ;Nelson PA;Pierres M;Fathman CG
通讯作者：
Fathman CG