Membrane Proximal Signaling in T lymphocytes: An interplay between co-operative processes and stochastic fluctuations
Departments of Pediatrics, Physics, Integrated Biomedical Sciences, The Ohio State University
(November 28, 2008 2:30 PM - 3:30 PM)
T lymphocytes (T cells) are the main orchestrators of our adaptive immune system. T cells can be activated by a minute number of molecular signatures of the pathogen, and this, in turn, can ultimately lead to the clearance of an infection. In spite of enormous advances in experimental technology and the availability of data at an unprecedented level of detail, the principles that govern the emergence of an immune response have proven elusive. This is principally because the pertinent processes involve highly co-operative dynamic events that are further modulated by stochastic fluctuations. A synergistic combination of theoretical, computational and experimental approaches can glean mechanistic insights into such complex phenomena. In this talk, I will describe how such synergies can work by focusing on two issues pertinent to T cell signaling and activation. The first concerns membrane proximal signaling events leading to Ras activation in T cells. In this context, I will describe how positive feedback loops result in thresholding and signal stability, and how this relates to thymic selection, a key process that shapes our self-tolerant T cell repertoire. I will also describe how stochastic fluctuations and competing positive and negative feedback regulation enable cells to make binary decisions that would not be possible in a mean-field world. Related phenomena concerning signal spreading revealed by computer simulations and field-theoretic formulations will be mentioned.