Structure-based design and evaluation of MHC class II binding peptides

Structural information regarding binding of peptides to the major histocompatibility complex (MHC) class II molecule is of great use for the design of compounds that intervene in the interaction between the MHC-peptide-T-cell receptor (TCR) complex. These compounds can be applied in the treatment of T-cell-mediated auto-immune disease for specific modulation of the disease process. In case no crystal structure of the MHC molecule is available, homology models of the MHC molecule can be of importance. Here we describe the construction of a homology model of the MHC class II molecule and binding of the peptide, that are involved in experimental auto-immune encephalomyelitis, a rat model for human multiple sclerosis. The validity of the model was investigated using experimental data of peptides binding to this MHC molecule.