Aldehyde-mannan antigen complexes target the MHC class I antigen-presentation pathway.
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.
Apostolopoulos
V
V
The Austin Research Institute, Heidelberg, Australia. v.apostolopoulos@ari.unimelb.edu.au
Pietersz
G A
GA
Gordon
S
S
Martinez-Pomares
L
L
McKenzie
I F
IF
D000447:Aldehydes / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D016466:CHO Cells; D002154:Calpain / Q000037:antagonists & inhibitors; D002401:Cathepsin B / Q000494:pharmacology; D002478:Cells, Cultured; D006224:Cricetinae; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D011992:Endosomes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D008351:Mannans / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018396:Mucin-1 / Q000276:immunology*; D009097:Multienzyme Complexes; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex; D011956:Receptors, Cell Surface / Q000276:immunology; D012545:Schiff Bases / Q000276:immunology
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D007976:Leupeptins; C116055:MUC1 tandem repeat peptide; D008351:Mannans; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D018396:Mucin-1; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D012545:Schiff Bases; C089487:acetyl-leucinyl-leucinyl-methional; C063261:acetylleucyl-leucyl-norleucinal; D002154:Calpain; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex