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

Vasso Apostolopoulos*, Geoffrey A. Pietersz, Siamon Gordon, Luisa Martinez-Pomares, Lan F.C. McKenzie

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

104 Scopus citations

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 1000 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.

Original languageEnglish
Pages (from-to)1714-1723
Number of pages10
JournalEuropean Journal of Immunology
Volume30
Issue number6
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Aldehyde
  • Antigen presentation
  • Cytotoxic T lymphocyte
  • Immunotherapy
  • Mannose receptor

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