Perspectives for computer modeling in the study of T cell activation.
The T cell receptor (TCR) is responsible for discriminating between self- and foreign-derived peptides, translating minute differences in amino-acid sequence into large differences in response. Because of the great variability in the TCR and its ligands, activation of T cells by foreign peptides is a quantitative process, dependent on a mix of upstream signals and downstream integration. Accordingly, quantitative data and computational models have shed light on many important aspects of this process: molecular noise in ligand recognition, spatial dynamics in T cell-APC (antigen presenting cell) interactions, graded versus all-or-none decision making by the TCR apparatus, mechanisms of peptide antagonism and synergism, and the tunability and robustness of activation thresholds. Though diverse in their formalism, these studies together paint a picture of how modeling has shaped and will continue to shape understanding of T cell immunobiology.
Coward
Jesse
J
Programs in Computational Biology and Immunology, ImmunoDynamics Group, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Germain
Ronald N
RN
Altan-Bonnet
Grégoire
G
D003198:Computer Simulation; D008213:Lymphocyte Activation / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*