The Kinetics of Immune Cell Receptor Binding Influence Immune Cell Signaling

Associated People:

Daniel Coombs (University of British Columbia)

Omer Dushek (Oxford University)

Milos Aleksic (Oxford University)

Richard J. Wheeler (Oxford University)

Hao Zhang (Oxford University)

Shaun-Paul Cordoba (Oxford University)

Yan-Chun Peng (Oxford University)

Ji-Li Chen (Oxford University)

Vincenzo Cerundolo (Oxford University)

Tao Dong (Oxford University)

Philip Anton van der Merwe (Oxford University)

Associated Sites:
PIMS University of British Columbia
Associated PIMS Programs:

IGTC in Mathematical Biology

T cells are essential players in the immune response to pathogens such as viruses and bacteria. They can be activated to respond when they recognize molecular signatures of infection (antigens) on the surface of antigen-presenting-cells of the immune system. The T cell response is highly specific (a particular T cell responds to only the right antigen), sensitive (a T cell will respond to as few as 1–10 antigens on a single cell) and speedy (antigen binding may induce signalling within just a few seconds). We use mathematical models to complement experimental data, seeking to understand how a T cell, using its surface antigen receptors, is able perform this task. We developed reaction-diffusion models of antigens binding and unbinding from T cell surface receptors and used them to interpret data on T cell activation in vitro. Our models and analysis strongly support the hypothesis that T cells can discriminate antigens based on both their binding and unbinding rates from the T cell antigen receptor.

References
  • O. Dushek, M. Aleksic, R. J. Wheeler, H. Zhang, S.-P. Cordoba, Y.-C. Peng, J.-L. Chen, V. Cerundolo, T. Dong, D. Coombs, P. A. van der Merwe Antigen Potency and Maximal Efficacy Reveal a Mechanism of Efficient T-Cell Activation Science Signaling, 4:ra39 (2011)
  • M. Aleksic, O. Dushek, H. Zhang, E. Shenderov, J.-L. Chen, V. Cerundolo, D. Coombs and P.A. van der Merwe Dependence of T Cell Antigen Recognition on TCR/pMHC Confinement Time Immunity, 32(2):163-174 (2010)