Aldehyde-mannan antigen complexes target the MHC class I antigen-presentation pathway

Antigens such as MUC1 coupled to oxidized mannan lead to rapid and efficien t MHC class I presentation to CD8(+) cells and a preferential T1 response; after reduction there is class II presentation and a T2 immune response. We now show that the selective advantage of the oxidized mannan-MUC1 is due t o the presence of aldehydes and not Schiff bases, and that oxidized mannan- MUC1 binds to the mannose and not scavenger receptors and is internalized a nd presented by MHC class 1 molecules 1000 times more efficiently than when reduced. After internalization there is rapid access to the class I pathwa y via endosomes but not lysosomes, proteasomal processing and transport to the endoplasmic reticulum, Golgi apparatus and cell surface. Aldehydes caus e rapid entry into the class 1 pathway, and can therefore direct the subseq uent immune response.