Structural basis of immunogenicity.

The most important 'on-off' switch within the immune system are the T cells: these decide whether an immune response has to be induced and maintained or not. Since T cells glean their information from the interaction between their specific T cell receptor and a MHC-peptide complex, MHC molecules are invaluable information carriers. Each T cell is usually restricted to only one of the set of autologous MHC molecules, but it is nevertheless able to react upon contact with allogeneic MHC. For a given T cell, both the MHC molecule and presented peptide thus play a crucial role in antigen recognition. MHC molecules govern the allele-specific restriction of T cells or, most important in transplantation immunology, allo-specific recognition, which is often peptide-independent. Peptides serving as MHC ligands are able either to tolerise T cells if presented under certain circumstances, or to activate T cells if presented by professional antigen-presenting cells in an inflammatory environment. The vast polymorphism of human MHC molecules combined with the complexity of thousands of different peptides presented by each allelic product provide the utmost heterogeneity. During the past few years, a huge amount of information about MHC-bound peptides has been compiled that helps us to understand the structural basis of immunogenicity. This contribution describes the characteristics of antigen processing within the MHC class I pathway, from proteasomal processing to the rules of MHC binding. Our current knowledge enables the exact description of many processes within the class I processing pathway and paves the way for the prediction of potential T cell epitopes by employing the rules of peptide presentation.