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 epidermis with unique morphological and molecular properties that enable their function as "sentinels" of the immune system. DCs are pivotal in the initiation and regulation of primary MHC class I restricted T lymphocyte immune responses and are able to present both endogenous and exogenous antigen onto class I molecules. Here, we study the MHC class I presentation pathway following activation of immature, CD34-derived human Langerhans cells by lipopolysaccharide (LPS). LPS induces an increase in all components of the MHC class I pathway including the transporter for antigen presentation (TAP), tapasin and ERp57, and the immunoproteasome subunits LMP2 and LMP7. Moreover, in CD34-derived Langerhans cells, the rapid increase in expression of MHC class I molecules seen at the cell surface following LPS activation is because of mobilization of MHC class I molecules from HLA-DM positive endosomal compartments, a pathway not seen in monocyte-derived DCs. Mobilization of class I from this compartment is primaquine sensitive and brefeldin A insensitive. These data demonstrate the regulation of the class I pathway in concert with the maturation of the CD34-derived Langerhans cells and suggest potential sites for antigen loading of class I proteins.
MacAry
P A
PA
Division of Immunology, Department of Pathology, Wellcome Trust Center for Molecular Mechanisms in Disease, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, United Kingdom.
Lindsay
M
M
Scott
M A
MA
Craig
J I
JI
Luzio
J P
JP
Lehner
P J
PJ
D018952:Antigens, CD34 / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D004347:Drug Interactions; D011992:Endosomes / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D018613:Microscopy, Confocal; D010641:Phenotype; D011319:Primaquine / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology
D018952:Antigens, CD34; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D011319:Primaquine