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Dr José A Villadangos

The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade, Melbourne, Victoria
Email: villadangos@wehi.edu.au
Tel: +61-3-9345-2532
Fax: +61-3-9347-0852

Roles of endosomal proteases and cystatins in dendritic cells (DC)
Dendritic cells (DC) are a specialyzed population of leukocytes that play a central role in the initiation of immune responses. DC capture pathogens in peripheral tissues and degrade them in intracellular compartments to generate small peptides. The DC then travel to the lymph nodes, where they display on their plasma membrane the pathogen peptides for recognition by T cells, a process termed antigen presentation. The T cells are then activated and an immune response against the pathogen ensues. My laboratory is interested in the roles played by the proteases contained in the endosomal compartments of DC (cathepsins) and by a family of protease inhibitors (cystatins) in antigen presentation. Both cathepsins and cystatins may also play important roles in remodeling of the extracellular matrix during DC trafficking from peripheral tissues to the lymph nodes. Identification of the cathepsins and cystatins expressed by DC, and characterization of their functions, might lead to development of novel drugs with modulatory properties on the proteolytic activities of DC. Such drugs could have applications for the improvement of vaccines and for the treatment of inflammatory processes, allergic reactions and autoimmune disorders.
Prof. Ken Shortman (WEHI, Melbourne)
Dr. Li Wu (WEHI, Melbourne)
Dr. E. Maraskovsky (Ludwig institute and CSL, Melbourne)
Dr. William Heath (WEHI, Melbourne)
Dr. Frank Carbone (University of Melbourne)
*Dr. Joseph Trapani (Peter MacCallum Cancer Center, Melbourne)
*Prof. H. Ploegh (Harvard Medical School, Boston, USA)
*Dr. Matt Bogyo (Stanford University Medical School)
*Prof. Christoph Peters (University of Freiburg, Germany)
*Dr. Thomas Reinheckel (University of Freiburg, Germany)
*Prof. Anders Grubb (University of Lund, Sweden)

(*collaborators working on a protease-related field)
J. A. Villadangos, R. J. Riese, C. Peters, H. A. Chapman, and H. L. Ploegh. 1997. "Degradation of mouse invariant chain: roles of cathepsins S and D and the influence of major histocompatibility complex polymorphism". J. Exp. Med. 186: 549-560.

J. Deussing, W. Roth, C. Peters, H. L. Ploegh, and J. A. Villadangos. 1998. "Cathepsins B and D are dispensable for MHC class II-mediated antigen presentation". Proc. Natl. Acad. Sci. USA. 95: 4516-4521.

J. A. Villadangos, C. Driessen, G. P. Shi, H. A. Chapman and H. L. Ploegh. 2000. "Early endosomal maturation of MHC class II molecules independently of cysteine proteases and H-2DM". EMBO J. 19: 882-891.

J. A. Villadangos and H. L. Ploegh. 2000. "Proteolysis in MHC class II antigen presentation: whos in charge?". Immunity. 12: 233-239.

J. A. Villadangos, M. Cardoso, R. Steptoe, D. van Berkel, J. Pooley, F. R. Carbone and K. Shortman. 2001. "MHC class II expression is regulated in dendritic cells independently of invariant chain degradation". Immunity. 14: 739-749.

D. El-Sukkari, N. S. Wilson, K. Hakansson, R. J. Steptoe, A. Grubb and J. A. Villadangos. 2003. Â?The protease inhibitor Cystatin C is differentially expressed among dendritic cell populations, but does not control MHC class II antigen presentationÂ?. J. Immunol. 171: 5003-5011.

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