Non Classical Endosomal Compartments Play Important Roles in Cross-Presentation by Dendritic Cells

Major histocompatibility complex class I (MHC I) molecules are expressed on the surface of all nucleated cells associated with short antigenic peptides about ten amino acids long at their extracellular part. The antigenic peptides are derived from endogenous proteins, which are processed by the ubiquitin-proteasome system in the cytosol. In contrast, exogenous proteins are processed by lysosomal proteases and resultant antigenic peptides are presented upon Major histocompatibility complex class II (MHC II) molecules. In several kinds of cells, especially in dendritic cells (DCs), exogenous proteins are processed and presented upon MHC I in addition to MHC II. This phenomenon is called crosspresentation (CP). CP plays important roles not only in activations of CD8+ T cells into cytotoxic T lymphocytes (CTLs) against anti-infectious and anti-tumor immunity but also in in-activations of self-acting CD8+ T cells by T cell energy or T cells deletion for peripheral tolerance. To this date, because of the important roles for CP, there are accumulating evidence to elucidate the molecular mechanisms of CP. Recent researches indicated that the endoplasmic reticulum (ER)- associated degradation (ERAD) pathway plays a central role in processing of exogenous proteins. The conveyances of exogenous proteins into ERAD-possible compartments are dependent upon the integration among endosomal or phagosomal membrane with ER membrane. But there still remain several important questions about CP, such as the precious molecular mechanisms of these integrations and the peptide-loading mechanisms upon MHC I. This review describes the recent researches about the molecular mechanisms of CP.