Fig. 2
From: A window of opportunity for cooperativity in the T Cell Receptor
TCRs are in transit between three different states of conformations. a Cartoon of the Resting, Active and Inhibited states. Blue and red arrows suggest a possible movement of the αβ ectodomains. Adoption of the three states is also reflected by movements of the cytoplasmic tails of the CD3 subunits. One of these movements results in exposure of the APA1/1 epitope in CD3ε. b A mathematical model with just two states (Resting and Active) cannot explain the optimum time point for the Active conformation shown in Fig. 1d, e. Rather, Active conformation reaches a plateau of indefinite duration. c Summary of reactions included in the model. The letters R, A and I stand for the states Resting, Active and Inhibited. A nanocluster of three TCRs and a trimeric pMHC ligand were chosen for modelling. The numerical values of the parameters and an explanatory description of the states are summarised in Methods. The plus symbols stand for either empty or non-crosslinked bound ligand used for conciseness. d Model to explain how ligation of two or more TCRs by pMHC results in stabilisation of the Active conformation in the entire TCR nanocluster. Adoption of the Active conformation by unbound TCRs facilitates their binding to additional pMHC ligands. e Numerical integration of the 3-state model after addition of ligand. The right panel shows the existence of an optimum of the Active conformation (red circles), even though binding has not yet reached saturation. This behaviour reflects the experimental results in Fig. 1d–e. f Prediction of the existence of cooperative effects on pMHC ligand binding derived from the mathematical model. Preincubation of TCR nanoclusters with free ligand at different times displays an optimum cooperation at the time when the maximal number of TCR nanoclusters in the Active conformation is found (Figs. 1d, e and 2e)
