Pseudomonas exotoxin-mediated delivery of exogenous antigens to MHC class I and class II processing pathways.
Peptides associated with class II MHC molecules are normally derived from exogenous proteins, whereas class I MHC molecules normally associate with peptides from endogenous proteins. We have studied the ability of Pseudomonas exotoxin A (PE) fusion proteins to deliver exogenously added antigen for presentation by both MHC class I and class II molecules. A MHC class II-restricted antigen was fused to PE; this molecule was processed in a manner typical for class II-associated antigens. However, a MHC class I-restricted peptide fused to PE was processed by a mechanism independent of proteasomes. Furthermore, we also found that the PE fusion protein was much more stable in normal human plasma than the corresponding synthetic peptide. We believe that effective delivery of an antigen to both the MHC class I and class II pathways, in addition to the increased resistance to proteolysis in plasma, will be important for immunization.
Lippolis
J D
JD
Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA.
Denis-Mize
K S
KS
Brinckerhoff
L H
LH
Slingluff
C L
CL
Galloway
D R
DR
Engelhard
V H
VH
D036002:ADP Ribose Transferases; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins; D005098:Exotoxins / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D011384:Proinsulin / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured; D037521:Virulence Factors; D058951:gp100 Melanoma Antigen; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000941:Antigens; D000951:Antigens, Neoplasm; D001427:Bacterial Toxins; D005098:Exotoxins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011384:Proinsulin; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D058951:gp100 Melanoma Antigen; D000097668:Pseudomonas aeruginosa Exotoxin A; C548637:PMEL protein, human; C548642:Pmel protein, mouse