U725: BIOLOGY OF HUMAN DENDRITIC CELLS (Director: Dr Daniel Hanau)
The team is composed of eleven persons, two of whom have a medical background and the others scientific qualifications in immunology, biochemistry, biology or biotechnologies.
The group includes three research workers "authorized to direct research" and is a host laboratory for the Diplomas (DEA) of Molecular and Cellular Biology and Molecular and Cellular Pharmacology of the University Louis Pasteur of Strasbourg and for the DEA of Organ Transplantation and Tissue Grafting of the University of Franche-Comté (Besançon).
The team also trains doctoral students, hosts post-doctoral workers and participates in the teaching of immunology at the Universities of Strasbourg, Paris VII and Tours .
As indicated by the title of the team, the research centres around human dendritic cells, namely those of the epidermis, Langerhans cells and dendritic cells differentiated in vitro from (i) monocytic precursors obtained from peripheral blood or (ii) CD34+ haematopoietic progenitors obtained from peripheral or umbilical cord blood.
In the past, the group has used molecular and cellular biology and immunology techniques to study the biochemical and cellular properties of: (i) antigen presenting molecules (MHC class II molecules, HLA-DR and CD1a and CD1b molecules) and (ii) proteins involved in antigen presentation. Among these molecules one finds "receptors" like RFcγRII /CD32 (transmembrane or soluble), RFcεRI , receptors common to the stress molecules Hsp60 and Hsp70, present on dendritic cells derived from monocytes, the langerin of epidermal Langerhans cells and also CD1e. Finally, the team has had the opportunity of studying deficits in peptide transporter (TAP) molecules.
It has likewise been possible to identify the so-called "recycling" endosomal compartment as being the compartment of Langerhans cells from which Birbeck granules form. These cytoplasmic organelles unique to Langerhans cells are the site of accumulation of langerin and CD1a molecules.
In addition, we have studied the effects of the infection of dendritic cells with a vaccinia virus ( Copenhagen or MVA strain).
At present, the team is concentrating its efforts on:
(i) CD1e, where we are attempting:
- to define its exact intracellular pathway, from the endoplasmic reticulum to the late endosomes/ lysosomes in dendritic cells;
- to identify the domains of the molecule implicated in its targeting to endosomes;
- to identify the cellular compartment in which it is solubilized (CD1e, synthesized in a transmembrane form in the endoplasmic reticulum, in fact becomes soluble in endosomal compartments, while following a purely intracellular pathway);
- to define the role of an N-terminal propeptide and to identify the cellular compartment in which it is cleaved from the molecule;
- to determine the function of CD1e in the anti-microbial immune response.
(ii) Birbeck granules, where we are attempting:
- to identify the components of the molecular machinery (Rab molecules) responsible for the traffic of langerin and for the biogenesis of Birbeck granules in epidermal Langerhans cells;
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M10-22E (Langerin+) : Effect of mutant GFP-Rab11- GTP
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- to define their eventual role in the transmission of antigenic information from langerin to CD1a molecules.
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