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Quicker Peptide Loading

Major histocompatibility complex (MHC) class II molecules are involved in presenting extracellular peptide antigens for surveillance by T cells. The peptides are loaded onto class II MHC molecules in the cytoplasm after which they migrate to the plasma membrane and present the peptides to CD4+ T cells. Studies have shown that certain organic compounds, such as aliphatic alcohols and phenol derivatives, can accelerate peptide loading onto class II MHC molecules, thereby amplifying the immune response.

Adamantine derivatives bind to a pocket in MHC molecules.

In this Paper of the Week, Sabine Höpner and colleagues screened a library of approximately 20,000 compounds to determine the molecular basis of this catalysis. They discovered that adamantine derivatives strongly accelerate the peptide-loading rate. Residue 86 on the MHC class II -chain was identified as the molecular target for this class of compounds, thereby supporting one general mechanism for ligand exchange catalysis unique to these molecules. The authors also elucidated both the structures of the catalytic compounds and the location of their target site, providing a structural framework for the rational design of new compounds to enhance vaccine antigen loading onto MHC class II molecules. This study also suggests a novel mechanism by which environmental factors may influence the induction of allergies or autoimmune diseases.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 38535-38542

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