Sayak Mukherjee
The process that warrants the generation of self tolerant peripheral T cells is called the thymocyte selection. During this maturation process, the overtly self reactive as well as unresponsive thymocytes are deleted from the cell population. The thymocytes equipped with T cell receptors (TCRs), capable of responding moderately to the self peptides are allowed to survive. Recently water soluble second messenger, inositol(1,3,4,5) tetrakisphosphate (IP4), has been implicated to play a crucial role in thymocyte positive selection (Huang et al.). It has been suggested that these IP4 molecules regulate the transient activation of the Tec- family protein tyrosine kinase Itk through a competing positive and negative feedbacks. The exact molecular mechanism involved in this feedback is however unclear. It is possible to con- struct more than one model with contrasting molecular mechanisms to explain the present body of experimental observations. This calls for criteria to choose among these models.
Robustness in face of the variation of the parameters in a model has been ubiquitously used as a criterion for model discrimination. Here we have used the maximum entropy, calculated with the constraints imposed by the experiments as a measure of robustness. Our data indicates that the models which are maximally robust share a cooperative allosteric mode of Itk regulation involving dimeric PH domains.
Joint work with Stephanie Rigaud, S. Seok, Agnieszka Prochenka, Guo Fu, Michael Dworkin, Nicholas R. J. Gascoigne, Veronika J. Vieland, Karsten Sauer, and Jayajit Das.
