Structural immunoinformatics : understanding MHC-Peptide-TR binding

Adaptive immune responses are governed by major histocompatibility complexes (MHC) binding to specific short antigenic peptides and then this peptide bound major histocompatibility complex (pMHC) being recognized by the T cell receptor (TR) which activates the T cells. The use of critical sequence-structure-function information to understand the principles underlying MHC specific peptide binding is well established and the focus is now on understanding TR recognition of pMHC complexes. Three-dimensional X-ray structures of pMHC complexes bound to the TR that are today characterized in good numbers facilitate structural analysis further. It is thus possible to predict potential T cell epitopes for vaccine design by utilizing information derived from available experimental structures which offer an alternative to sequence-based approaches that require large dataset for training. In this chapter, we introduce the use of structural data, a comparative modeling and docking protocol for epitope prediction for specific MHC alleles and also compare the results of our experiments on different disease-specific alleles. We also talk about the possibilities of predicting how well a pMHC complex can bind to the TR.17 page(s