Regulation of MHC class I transport in human dendritic cells and the dendritic-like cell line KG-1.
Dendritic cells (DCs) progress through distinct maturational phases; immature DCs capture Ag while mature DCs are optimized for Ag presentation. Proper control of immunity requires regulated compartmentalization of MHC class II molecules. We report that DCs also regulate MHC class I trafficking throughout maturation. Although mature human DCs express high levels of surface MHC class I, immature DCs exhibit lower surface levels while retaining MHC class I-peptide complexes in the Golgi. A cell line, KG-1, behaves similarly. We confirm the similarity of KG-1 to DCs by demonstrating its capacity to present exogenous Ags in an MHC class I-restricted fashion to CD8(+) T cell hybridomas, a phenomenon called cross-presentation. Biochemical characterization of MHC class I trafficking throughout maturation showed that, in early KG-1 dendritic-like cells, surface arrival of MHC class I-peptide complexes is delayed by their retention in the Golgi. In mature dendritic-like cells, these complexes relocate to the surface and their stability increases, concomitant with up-regulation of costimulatory molecules. Maturation induces qualitative changes in the MHC class I-associated peptide repertoire demonstrated by increased thermostability. The differential processing of MHC class I throughout maturation may prevent premature immune activation while promoting T cell responses in lymph nodes to Ags acquired at sites of inflammation.
Ackerman
Anne L
AL
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Cresswell
Peter
P
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D019281:Dimerization; D004527:Egg Proteins / Q000276:immunology / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000096:biosynthesis / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000378:metabolism
D004527:Egg Proteins; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D010455:Peptides; D001613:beta 2-Microglobulin; D010047:Ovalbumin