Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MHC

Ilaria Potolicchio, Sriram Chitta, Xiaonan Xu, Dora Fonseca, Giovanna Crisi, Vaclav Horejsi, Jack L. Strominger, Lawrence J. Stern, Graca Raposo, Laura Santambrogio

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28 Scopus citations

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-espressing surface empty HLA-DR were found in T cell areas of secondary lymphoid organs.

Original languageEnglish (US)
Pages (from-to)4935-4947
Number of pages13
JournalJournal of Immunology
Volume175
Issue number8
StatePublished - Oct 15 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Potolicchio, I., Chitta, S., Xu, X., Fonseca, D., Crisi, G., Horejsi, V., Strominger, J. L., Stern, L. J., Raposo, G., & Santambrogio, L. (2005). Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MHC. Journal of Immunology, 175(8), 4935-4947.