GCB2011 Junior Paper Modeling the Variable Regions of T-Cell Receptors

Heterodimeric T-cell receptors (TCR) bind and recognize pathogenic molecules presented by major histocompatibility complex (MHC) molecules. The relative orientation of the two TCR chains can differ depending on their type. Here we present a comprehensive analysis of this phenomenon based on the current set of known TCR X-ray structures. During the analysis the structures could be grouped into several clusters. Based on these structural results, we developed a method to predict the TCR chain association. Such a prediction is e.g. important to reduce complications in adoptive T-cell therapy. Furthermore, the orientation might be important for the TCR:peptide:MHC (TCR-p-MHC) complex formation.