title: Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation.
abstract: HLA-E is a nonclassical HLA-class I molecule whose best known role is to protect from the natural killer cells. More recently, an additional function more similar to that of classical HLA-class I molecules, i.e., antigen presentation to T cells, is emerging. However, much remains to be explored about the intracellular trafficking of the HLA-E molecules. With the use of 3 different cellular contexts, 2 monocytic cell lines, U937 and THP1, and peripheral blood monocytes, we show here a remarkable increase of HLA-E during monocyte-macrophage differentiation. This goes independently from the classical HLA-class I, the main source of HLA-E-specific peptides, which is found strongly up-regulated upon differentiation of peripheral blood monocytes but not at all in the case of U937 and THP1 cell lines. Although in all cases, there was a moderate increase of HLA-E expressed in the cell surface, lysis by natural killer cells is comparably restored by an anti-NKG2A antibody in untreated as well as in PMA-differentiated U937 cells. Instead, the great majority of the HLA-E is retained in the vesicles of the autophagy-lysosome network, where they colocalize with the microtubule-associated protein light chain 3, as well as with the lysosomal-associated membrane protein 1. We conclude that differently from the classical HLA-class I molecules, the primary destination of the newly synthesized HLA-E molecules in macrophages is, rather than the cell membrane, the intracellular autophagy-lysosomal vesicles where they are stored and where they can encounter the exogenous antigens.
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy giorgio.camilli@uniroma1.it.
authors: Giorgio
authors: G
authors: Camilli
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Antonino
authors: A
authors: Cassotta
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Simone
authors: S
authors: Battella
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Gabriella
authors: G
authors: Palmieri
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Angela
authors: A
authors: Santoni
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Fabiana
authors: F
authors: Paladini
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Maria Teresa
authors: MT
authors: Fiorillo
authors: Departments of *Biology and Biotechnology "Charles Darwin," Experimental Medicine, and Molecular Medicine, and Institute Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
authors: Rosa
authors: R
authors: Sorrentino
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation; D042541:Intracellular Space / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport; D015854:Up-Regulation; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D045726:Metalloproteases; D000097625:HLA-E Antigens
keywords: NK cells; human leukocyte antigen-E; monocytic