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 e xogenous proteins, whereas class I MHC molecules normally associate with pe ptides from endogenous proteins. We have studied the ability of Pseudomonas exotoxin A (PE) fusion proteins to deliver exogenously added antigen for p resentation by both MHC class I and class II molecules. A MHC class II-rest ricted antigen was fused to PE; this molecule was processed in a manner typ ical for class II-associated antigens. However, a MHC class I-restricted pe ptide 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. (C) 2000 Academic Press.