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

• Published in: European journal of immunology Vol. 30; no. 6; pp. 1714 - 1723
• Main Authors: Apostolopoulos, Vasso, Pietersz, Geoffrey A., Gordon, Siamon, Martinez‐Pomares, Luisa, McKenzie, Ian F.C.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.06.2000
• Subjects: Aldehyde; Aldehydes - immunology; Animals; Antigen presentation; Antigen Presentation - drug effects; Antigen Presentation - immunology; Calpain - antagonists & inhibitors; Cathepsin B - pharmacology; CD8 antigen; Cells, Cultured; CHO Cells; Cricetinae; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors - pharmacology; Cytotoxic T lymphocyte; Endosomes - immunology; Histocompatibility Antigens Class I - immunology; Humans; Immunotherapy; Lectins, C-Type; Leupeptins - pharmacology; Lysosomes - immunology; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - immunology; mannan; Mannans - immunology; Mannose receptor; Mannose-Binding Lectins; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; MUC-1 antigen; Mucin-1 - immunology; Multienzyme Complexes; Oxidation-Reduction; Peptide Fragments - immunology; Proteasome Endopeptidase Complex; Receptors, Cell Surface - immunology; Schiff Bases - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200006)30:6<1714::AID-IMMU1714>3.0.CO;2-C

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.