T cell activation and proliferation

by Amir Erez

at Condensed Matter Theory Seminar

Wed, 16 Mar 2016, 13:30
Physics building (#54) room 207

Abstract

T cells have unique receptors that recognize specific antigenic fragments usually derived from pathogens with exquisite specificity Adaptive immunity relies on such correct recognition of non self to reach a decision whether or not to mount an immune response to eliminate the antigen In this context cancer can be thought of as a failure of the immune system to recognize and attack a serious threat Accordingly understanding and subsequently manipulating T cell recognition of cancer tumors provides a promising direction in cancer care When a T cell encounters its pre programmed antigen it initiates a response which can be roughly divided to three stages stretching over three time scales: i Within minutes: initiation of an enzymatic signaling cascade which transfers information from the surface T cell receptor to the nucleus ii Within hours: activation of cellular programs which prepare the cell to proliferate iii Within days: activated T cells enter cell cycle and start proliferating vigorously In this study we develop a precise and robust assay to quantify these three stages of T cell response: signaling activation and proliferation We use our assay to show how by controlling the stimulus strength either by antigen dose or affinity we can predict and control the strength of immune response at all three stages We inhibit different parts of the signaling cascade using small molecule drugs and dissect how the inhibited signaling affects the activation and proliferation stages of the T cell program Finally we combine our quantitative observations to answer a much sought out question the question of antigen sensing: given a T cell population and an unknown antigen of unknown dose just how antigenic is it The ability to correctly sense antigenicity has important ramification for immune based cancer therapies under development today Interestingly even in such a simple biological study one quickly encounters open questions in the physics of stochastic systems In the talk I will point out several such questions where the experimental observations motivate a deeper theoretical understanding of the stochastic dynamics of living things

Created on 24-02-2016 by Bar Lev, Yevgeny (ybarlev)
Updaded on 24-02-2016 by Bar Lev, Yevgeny (ybarlev)