Theory of Antigen Encoding and Cross-receptor Interactions in T Cell Immunotherapy

Event Details

Type

Center for Studies in Physics and Biology Seminars

Speaker(s)

Francois Bourassa, Ph.D. candidate, McGill University

Speaker bio(s)

The mechanisms connecting early T cell receptor (TCR) activation to complex T cell responses in the immune system have not been fully elucidated. Understanding these processes quantitatively is however crucial to fine-tune immunotherapy treatments against cancer. To systematically map out T cell activation, the lab of Grégoire Altan-Bonnet has developed a robotic platform which tracks over days the dynamics of messenger proteins, called cytokines, produced by T cells to communicate with other cells. We found a low-dimensional representation of high-dimensional cytokine dynamics in which trajectories are ordered according to antigen strength. We termed this property “antigen encoding” and quantified it using information theory and nonlinear dynamical equations. We then leveraged these insights to disentangle cross-receptor interactions in chimeric antigen receptor (CAR) T cells used in cancer immunotherapy. In particular, we developed an adaptive model of receptor proofreading to explain antagonism (i.e. inhibition) of CAR activation by weak TCR stimulation. Our model predictions quantitatively matched experimental data, enabling us to engineer antagonism to reduce CAR T cell toxicity against healthy tissues.

Open to

Tri-Institutional