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A unifying mathematical framework for experimental TCR-pMHC kinetic constants

J. Faro, M. Castro, C. Molina-Paris

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.


Palabras clave: Computational models; Kinetics; Lymphocyte activation


Scientific Reports. Volumen: 7 Numero: 46741

Índice de impacto JCR y cuartil: 4.122 - Q1 (2017)

Referencia DOI: DOI icon 10.1038/srep46741    

Publicado on-line: Abril 2017.


    Líneas de investigación:
  • *Sistemas Mecánicos: Mecánica Estructural, Elementos de Máquinas, Prototipado Rápido, Metrología Dimensional

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