Loading of MHC Class I and II Presentation Pathways by Exogenous Antigens: A Quantitative In Vivo Comparison

The MHC class I pathway is usually fueled by endogenous Ags, while exogenous Ags reach the MHC class II pathway. Although exogenous epitopes may also enter the MHC class I pathway, quantification of the efficiency of the process has remained a difficult task. In an attempt of such a quantification, we directly compared the amount of exogenous virus-like particles required for induction of cytotoxic T cell responses by cross-priming with the amount of virus-like particles required for induction of Th cell responses by the conventional route of MHC class II loading as an internal standard. Surprisingly, we found that cross-presentation of peptides derived from exogenous Ags on MHC class I molecules is of only marginally lower efficiency ( approximately 1- to 10-fold) than the classical MHC class II pathway in vitro and in vivo. Thus, Ag quantities required for cross-presentation and cross-priming are similar to those required for fueling the MHC class II pathway.