Function and dysfunction of T cell receptor: structural studies

The engagement of the T cell receptor (TCR) to its ligand, the major histocompatibility complex (MHC)-peptide complex, leads to T cell activation. The molecular mechanisms leading to this activation are still unknown. Dimerization or substantial conformational changes following TCR ligation have not been observed by classical biochemical methods or by X-ray crystallography of the TCR/MHC complex. However, most of these experiments have used reductionist approaches in which only MHC and TCR molecules were taken into account. In fact, the TCR is only one of many molecules forming the TCR complex (TCRC), and the interplay among the components of this larger complex have not been studied in depth. The reconstitution of a complete TCRC using recombinant molecules is our goal and will be the first step to new structural and functional studies.