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Introduction

The dimerization of the extracellular receptor domains is a important necessity for the functionality of our modular receptor system. Presenting the system a stimulus in the form of spatial arranged ligands, the extracellular domains dimerize, thus the corresponding intracellular parts such as the split lactamase halves or split fluorescent proteins complement to measureable output. To analyse the theoretical functionality due to dimerization, first two receptor dimerization models (one T cell receptor model and one general receptor model) are introduced and discussed and then a proper model for the modular receptor system is constructed.

T cell receptor dimerization model I

T cells are a special type of white blood cells (lymphocytes) and play a central role in cell-mediated immunity. They carry special receptors, so called T cell receptors (TCR) on their membrane. One part of the mechanisms to activate a TCR and thus to activate a T Cell is the binding of a ligand, also called antigen, to the TCR. As research showed, one single ligand-TCR complex does not lead to a T cell response yet, as at least two ligand-TCR complexes and their dimerization seem to be required for proper T cell activation (Schamel, 2006; Bachmann 1999). In our case the ligands are nitro-iodo-phenol (NIP) molecules attached to a DNA-Origami structure at a (variable) distance of ~6nm to each other. These NIPs are recognized and bound by the TCRs. As the distance is small enough for two TCRs to approach very closely when each of them binds a NIP, they can dimerize.

Extracellular signaling

A simplified pathway shows the extracellular sequence of TCR activation. After the NIP binding two complexes come together and form a dimer which then leads to activaton of the TCR and further intracellular signaling and T cell activation.

Pathway of TCR dimerization