Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells

Langerhans cells are a subset of dendritic cells (DCs) found in the human e pidermis with unique morphological and molecular properties that enable the ir function as "sentinels" of the immune system. DCs are pivotal in the ini tiation and regulation of primary MHC class I restricted T lymphocyte immun e responses and are able to present both endogenous and exogenous antigen o nto class I molecules. Here, we study the MHC class I presentation pathway following activation of immature, CD34-derived human Langerhans cells by li popolysaccharide (LPS), LPS induces an increase in all components of the MH C class I pathway including the transporter for antigen presentation (TAP), tapasin and ERp57, and the immunoproteasome subunits LMP2 and LMP7, Moreov er, in CD34-derived Langerhans cells, the rapid increase in expression of M HC class I molecules seen at the cell surface following LPS activation is b ecause of mobilization of MHC class I molecules from HLA-DM positive endoso mal compartments, a pathway not seen in monocyte-derived DCs, Mobilization of class I from this compartment is primaquine sensitive and brefeldin A in sensitive. These data demonstrate the regulation of the class I pathway in concert with the maturation of the CD34-derived Langerhans cells and sugges t potential sites for antigen loading of class I proteins.