Several MHC-II complexes with known peptide epitopes of T-cell receptors have now been solved by X-ray crystallography. Specificity-pockets provide distinct peptide contacts that influence peptide conformation and define the binding register of immunogenic peptides within different allelic MHC- II molecules. Studies on T-cell activation and intracellular signal transduction have shown that altering TCR-contacts with peptide side-chains can drastically change the nature of the ensuing immune response. Here, we trace the path from a structural understanding of these phenomena to the design of new therapeutics toward the treatment of immunological diseases.
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