TY - JOUR
T1 - Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MHC
AU - Potolicchio, Ilaria
AU - Chitta, Sriram
AU - Xu, Xiaonan
AU - Fonseca, Dora
AU - Crisi, Giovanna
AU - Horejsi, Vaclav
AU - Strominger, Jack L.
AU - Stern, Lawrence J.
AU - Raposo, Graca
AU - Santambrogio, Laura
PY - 2005/10/15
Y1 - 2005/10/15
N2 - 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-espressing surface empty HLA-DR were found in T cell areas of secondary lymphoid organs.
AB - 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-espressing surface empty HLA-DR were found in T cell areas of secondary lymphoid organs.
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U2 - 10.4049/jimmunol.175.8.4935
DO - 10.4049/jimmunol.175.8.4935
M3 - Article
C2 - 16210595
AN - SCOPUS:26844505013
SN - 0022-1767
VL - 175
SP - 4935
EP - 4947
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -