BINDING INTERACTIONS WITHIN PEPTIDE-MHC COMPLEXES

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The objective of this research is to define the relative energetics of binding interactions between peptides and MHC class II proteins. Helper T cells are activated by the interaction of an antigen receptor on the T cell with ligands expressed on the surface of other cells. These ligands are complexes of peptides bound to MHC class II proteins. The peptide is bound in a groove on the membrane distal face of the protein. Binding interactions include an array of hydrogen bonds from MHC sidechains to the peptide backbone and pockets in the peptide-binding groove on which peptide sidechains reside. While much is known about the structure of these complexes, the relative contributions of the different binding interactions to the overall stabilities of the complexes are not unknown. We propose to systematically eliminate specific hydrogen-bond and pocket interactions for a variety of peptide-MHC complexes and evaluate their contribution the stabilities. These results will define the rules for peptide binding to MHC class II proteins. The binding rules will greatly aid analyses of antigenic peptide-MHC complexes and the identification of T-cell epitopes.