CLASS-I MHC PRESENTATION OF EXOGENOUS ANTIGENS

Class I MHC (MHC-I) molecules present primarily endogenous antigens, i .e. antigens that are present in the cytosol and are subject to the cy tosolic processing mechanisms that comprise the conventional MHC-I pro cessing pathway. However, exogenous antigens can also be presented by MHC-I molecules in certain circumstances, particularly in the case of particulate antigens. Recently, considerable attention has been focuse d on mechanisms that may contribute to alternate MHC-I processing path ways. Divergent results in several different systems have suggested th at more than one alternate processing mechanism may exist. After phago cytic or endocytic uptake, some exogenous nous antigens can escape the vacuolar system and penetrate into the cytosol, accessing the convent ional MHC-I antigen processing mechanisms. In other cases, MHC-I molec ules present antigens that have no clear ability to actively escape th e vacuolar system. Some results indicate that certain alternate proces sing mechanisms are quite distinct from the conventional MHC-I pathway and are not dependent on compartments, proteins, or mechanisms that a re necessary for the conventional pathway, including the endoplasmic r eticulum, the transporter for antigen presentation (TAP) and proteasom es. In vivo, alternate MHC-I processing mechanisms may be expressed pr imarily by phagocytic antigen presenting cells, i.e., macrophages, and perhaps dendritic cells, although other cell types may contribute in certain circumstances. These mechanisms may play important roles in ge nerating CD8 T cell responses, especially to antigens expressed by vac uolar microorganisms. In addition, they provide a potential avenue for therapeutic immunization to achieve protective CD8 T cell responses w ith nonviable vaccine preparations, in the absence of the endogenous a ntigen synthesis that is provided by live viral vaccine preparations.