Alam S M, Davies G M, Lin C M, Zal T, Nasholds W, Jameson S C, Hogquist K A, Gascoigne N R, Travers P J
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Immunity. 1999 Feb;10(2):227-37. doi: 10.1016/s1074-7613(00)80023-0.
The kinetics of interaction between TCR and MHC-peptide show a general relationship between affinity and the biological response, but the reported kinetic differences between antigenic and antagonistic peptides are very small. Here, we show a remarkable difference in the kinetics of TCR interactions with strong agonist ligands at 37 degrees C compared to 25 degrees C. This difference is not seen with antagonist/positive selecting ligands. The interaction at 37 degrees C shows biphasic binding kinetics best described by a model of TCR dimerization. The altered kinetics greatly increase the stability of complexes with agonist ligands, accounting for the large differences in biological response compared to other ligands. Thus, there may be an allosteric, as well as a kinetic, component to the discrimination between agonists and antagonists.
TCR与MHC-肽之间相互作用的动力学显示出亲和力与生物学反应之间的一般关系，但报道的抗原肽和拮抗肽之间的动力学差异非常小。在这里，我们展示了与25摄氏度相比，TCR在37摄氏度下与强激动剂配体相互作用的动力学存在显著差异。而拮抗剂/阳性选择配体则未观察到这种差异。37摄氏度下的相互作用表现出双相结合动力学，最好用TCR二聚化模型来描述。动力学的改变极大地增加了与激动剂配体形成的复合物的稳定性，这解释了与其他配体相比生物学反应的巨大差异。因此，在激动剂和拮抗剂之间的区分可能存在变构以及动力学成分。
