PMID- 12682250 OWN - NLM STAT- MEDLINE DCOM- 20030731 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 170 IP - 8 DP - 2003 Apr 15 TI - Regulation of MHC class I transport in human dendritic cells and the dendritic-like cell line KG-1. PG - 4178-88 AB - 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. FAU - Ackerman, Anne L AU - Ackerman AL AD - Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. FAU - Cresswell, Peter AU - Cresswell P LA - eng GR - AI10347-02/AI/NIAID NIH HHS/United States GR - AI23081/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Egg Proteins) RN - 0 (H-2 Antigens) RN - 0 (H-2Kb protein, mouse) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (OVA-8) RN - 0 (Peptide Fragments) RN - 0 (Peptides) RN - 0 (beta 2-Microglobulin) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Antigen Presentation MH - Antigen-Presenting Cells/cytology/immunology/metabolism MH - Cell Differentiation/immunology MH - Dendritic Cells/cytology/*immunology/*metabolism MH - Dimerization MH - Egg Proteins/immunology/metabolism MH - H-2 Antigens/immunology/metabolism MH - HLA Antigens/biosynthesis/metabolism MH - Histocompatibility Antigens Class I/biosynthesis/*metabolism MH - Humans MH - Kinetics MH - Mice MH - Models, Biological MH - Ovalbumin/immunology/metabolism MH - Peptide Fragments MH - Peptides/immunology/metabolism MH - Protein Binding/immunology MH - Protein Transport/immunology MH - Tumor Cells, Cultured/*immunology/*metabolism MH - beta 2-Microglobulin/biosynthesis/metabolism EDAT- 2003/04/12 05:00 MHDA- 2003/08/02 05:00 CRDT- 2003/04/12 05:00 PHST- 2003/04/12 05:00 [pubmed] PHST- 2003/08/02 05:00 [medline] PHST- 2003/04/12 05:00 [entrez] AID - 10.4049/jimmunol.170.8.4178 [doi] PST - ppublish SO - J Immunol. 2003 Apr 15;170(8):4178-88. doi: 10.4049/jimmunol.170.8.4178.