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

Apostolopoulos V, Pietersz GA, Gordon S, Martinez-Pomares L, McKenzie IF

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  • Journal European journal of immunology

  • Published 09 Aug 2000

  • Volume 30

  • ISSUE 6

  • Pagination 1714-23

  • DOI 10.1002/1521-4141(200006)30:6<1714::AID-IMMU1714>3.0.CO;2-C

Abstract

Antigens such as MUC1 coupled to oxidized mannan lead to rapid and efficient 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 to the presence of aldehydes and not Schiff bases, and that oxidized mannan-MUC1 binds to the mannose and not scavenger receptors and is internalized and presented by MHC class I molecules 1,000 times more efficiently than when reduced. After internalization there is rapid access to the class I pathway via endosomes but not lysosomes, proteasomal processing and transport to the endoplasmic reticulum, Golgi apparatus and cell surface. Aldehydes cause rapid entry into the class I pathway, and can therefore direct the subsequent immune response.