Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MIIC
Details
Serval ID
serval:BIB_3FFC75248152
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MIIC
Journal
Journal of Immunology
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
10/2005
Volume
175
Number
8
Pages
4935-47
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 15
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 15
Abstract
Dendritic cells (DC), uniquely among APC, express an open/empty conformation of MHC class II (MHC-II) proteins (correctly folded molecules lacking bound peptides). Generation and trafficking of empty HLA-DR during DC differentiation are investigated here. HLA-DR did not fold as an empty molecule in the endoplasmic reticulum/trans-Golgi network, did not derived from MHC/Ii complexes trafficking to the cell surface, but was generated after invariant chain degradation within lysosomal-like MHC-II rich compartments (MIIC). In pre-DC, generated from monocytes cultured in the presence of GM-CSF, Lamp-1(+)MHC-II(+) compartments are predominantly electron dense and, in these cells, empty MHC-II molecules accounts for as much as 20% of total surface HLA-DR. In immature DC, generated in presence of GM-CSF and IL-4, empty HLA-DR reside in multilamellar MIIC, but are scarcely observed at the cell surface. Thus, the morphology/composition of lysosomal MIIC at different DC maturational stages appear important for surface egression or intracellular retention of empty HLA-DR. Ag loading can be achieved for the fraction of empty HLA-DR present in the "peptide-receptive" form. Finally, in vivo, APC-expressing surface empty HLA-DR were found in T cell areas of secondary lymphoid organs.
Keywords
Amino Acid Sequence
Cell Differentiation/*physiology
Cell Membrane/*metabolism
Cells, Cultured
Dendritic Cells/*cytology/metabolism
Endoplasmic Reticulum/ultrastructure
Granulocyte-Macrophage Colony-Stimulating Factor
HLA-DR Antigens/metabolism
Histocompatibility Antigens Class II/*chemistry/metabolism
Humans
Interleukin-4/pharmacology
Lymphoid Tissue/metabolism
Lysosomes/*metabolism
Molecular Sequence Data
Monocytes/ultrastructure
Myeloid Cells/*cytology/metabolism
Peptides/metabolism
Protein Conformation
trans-Golgi Network/ultrastructure
Pubmed
Web of science
Create date
25/01/2008 15:16
Last modification date
20/08/2019 13:37