Qualitative and quantitative differences in T cell receptor binding of agonist and antagonist ligands

S. Munir Alam, G. Mark Davies, Lin Christina M., Zal Tomasz, Wade Nasholds, Stephen C. Jameson, Kristin A. Hogquist, Nicholas R.J. Gascoigne, Paul J. Travers

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

Abstract

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°C compared to 25°C. This difference is not seen with antagonist/positive selecting ligands. The interaction at 37°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.

Original languageEnglish (US)
Pages (from-to)227-237
Number of pages11
JournalImmunity
Volume10
Issue number2
DOIs
StatePublished - Feb 1999

Bibliographical note

Funding Information:
We thank F. Carbone (Monash University, Australia) for the TCR cDNA clones and Biotechnology Research Institute (National Research Council Canada) for the program SPRevolution. S. M. A is a Special Fellow of the Leukemia Society of America and T. Z. is a Fellow of the Human Frontier Science Program. S. C. J is supported by the American Cancer Society. This work was supported by grants from the National Institutes of Health (R01 GM39476, to N. R. J. G.) and the Medical Research Council, and aided by NATO collaborative research grant 970272. This is publication number 11383-IMM from The Scripps Research Institute.

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