Receptor binding and triggering are central in Immunology as T cells activated through their T cell receptors (TCR) by protein antigens orchestrate immune responses. In order to understand receptor-ligand interactions, many groups working with different experimental techniques and assays have generated a vast body of knowledge during the last decades. However, in recent years a type of assays, referred to as two-dimensional or membrane-to-membrane, has questioned our current understanding of the role of different kinetic constants (for instance, on- versus off-rate constants) on TCR-ligand interaction and subsequent T cell activation. Here we present a general mathematical framework that provides a unifying umbrella to relate fundamental and effective (or experimentally determined) kinetic constants, as well as describe and compare state-of-the-art experimental methods. Our framework is able to predict the correlations between functional output, such as 1/EC50, and effective kinetic constants for a range of different experimental assays (in two and three dimensions). Furthermore, our approach can be applied beyond Immunology, and serve as a «translation method» for the biochemical characterization of receptor-ligand interactions.
Keywords: Computational models; Kinetics; Lymphocyte activation
Scientific Reports. Volume: 7 Issue: 46741 Pages: 1-12
JCR Impact Factor and WoS quartile: 4.122 - Q1 (2017); 4.011 - Q1 (2018)
DOI reference: 10.1038/srep46741
Published on-line: April 2017.
J. Faro, M. Castro, C. Molina-Paris. A unifying mathematical framework for experimental TCR-pMHC kinetic constants. Scientific Reports. vol. 7, no. 46741, pp. 1-12, April 2017 [Online]