LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC).
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1
Medical University Vienna, Clinical Institute of Pathology, Austria
LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC).
Dario Leone* Renate Kain and Andrew Rees*
Clinical Institute of Pathology, Medical University of Wien.
Supported by Marie Curie action (Transvir network)
Keyword (Human Dendritic Cell, novel endocytic receptor, LAMP-2, uptake, antigen presentation)
Lysosome-associated membrane protein-2 (LAMP-2) is a type 2 membrane-protein that is commonly used as lysosome and late endosomal marker and with essential roles in chaperone mediated autophagy and antigen presentation. LAMP-2 is also present on the cell-surface although its role was never studied. We focus on the role of LAMP-2 as a receptor on freshly isolated monocytes and iDCs with possible implication in antigen presentation.
LAMP-2 was detected on the surface of immature MDDC both by FACS and confocal microscopy, its expression increased after maturation with IFN-γ LPS. The monoclonal anti-LAMP-2 antibody (H4B4) bound to LAMP-2 on the surface of MDDC and was rapidly and specifically internalized when compared to control antibodies in the presence of Fc blockade. Also the Fab fragment alone is internalized as well. Uptake was absent in MDDC from an individual with genetic LAMP-2 deficiency, Danon-disease. As expected, MDDC LAMP-2 and HLA-DR localized to partially overlapping compartments in iDC but there was no co-localization with HLA-DM. However, confocal microscopy showed that H4B4 transits into a HLA-DM positive compartment 1 hour after ligating LAMP-2 on the cell surface. Co-localization is no longer detectable after 3 hours. Finally, stimulation of immature MDDCs with H4B4 promote activation in the presence of IFN-γ indicated by up-regulation of CD80/CD83.
This data suggest that when LAMP-2 is on the membrane acts as a specific receptor for internalization of extracellular molecules. H4B4 mimics natural ligands and after internalization can be found into the MIIC causing as well the maturation of DCs up-regulating CD80/83.
Keywords:
human dendritic cell,
Antigen Presentation,
Lysosomes,
endocytic receptor,
autoan,
MHCII compartment
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune receptors and signaling
Citation:
Leone
D
(2013). LAMP-2, a novel endocytic receptor on human monocytes derived dendritic cells (MDDC)..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00633
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Dario Leone, Medical University Vienna, Clinical Institute of Pathology, Vienna, 1090, Austria, bleons2.0@gmail.com