Tracing the Route Taken by Peptides and Major Histocompatibility Complex Class I Molecules in Presentation of Exogenous Antigens

Since the discovery of cross priming by Bevan (1 ) nearly thirty years ago, a large amount of work has focused on defining the mechanisms that account for this in vivo phenomenon. Following the discovery that the majority of major histocompatibility complex (MHC-I)-bound peptides are derived from endogenous (intracellular) sources (2 ,3 ), a paradigm was established that exogenous (extracellular) antigens (Ags) are presented on MHC-I molecules and endogenous Ags are presented on MHC-II. In more recent years, accumulating evidence using a number of model systems, including presentation of bacterial (4 ,5 ), particulate (6 ) and soluble (7 ,8 ) Ag, has challenged that paradigm.