Immunology Graduate Group
Biomedical Graduate Studies
Yair Argon, Ph.D
Professor of Pathology and Laboratory Medicine Department: Pathology and Laboratory Medicine
Address: 816B Abramson Research Center
3615 Civic Center Boulevard
Philadelphia, PA 19104-4318
Office: (267) 426-5131
Fax: (267) 426-5165
Email: yargon@mail.med.upenn.edu
Education:
Ph.D. (Biochemistry)
Harvard Medical School, 1980.
B.S. (Biology)
The Hebrew University Medical School, Jerusalem, Israel , 1974.
Research Interests:
Antigen presentation, expression of antigen receptors and dendritic cell functions
Research Summary:
The two areas of research in our lab focus on the roles that molecular chaperones play in the immune system. The first area is antigen presentation by dendritic cells and in particular, the phenomenon of cross-presentation. Several molecular chaperones are peptide-binding proteins and this property can be utilized to augment weak T cell responses. When dendritic cells are allowed to internalize peptide-loaded chaperones, in particular glucose-regulated protein 94, T cells are activated at very low doses of peptide. Because this mode of presentation can in principle be used therapeutically, we study how dendritic cells take up GRP94 and other chaperones and the molecular requirements for efficient transfer of peptides from them to MHC molecules. In addition, we seek to determine the spectrum of peptides that are bound by GRP94 and calreticulin, and compare them to T cell antigenic peptides. We use dendritic cells from transgenic and knockout mice defective in aspects of endocytosis, proteolysis or MHC trafficking, as well as engineered versions of chaperones designed to alter their biochemical activities.
Our second area of interest is systemic amyloidosis, a disease where fragments of antibody molecules polymerize to form amyloid plaques that interfere with the function of many organs. Knowing that particular V regions are more susceptible to amyloid formation than others, we want to determine what kinds of somatic mutations lead to amyloid polymerization, to correlate gene sequences with susceptibility to this disease. We also study how molecular chaperones recognize the mutant antibodies, in order to inhibit this pathogenic polymerization. Using a cell-based model for amyloid formation, we study how manipulating the cellular stress responses affect the aggregation of antibodies, and we are in the process of generating a mouse model for this disease.
Recent Publications
Davis, D., R. Raffen, J.L. Dul, S. Vogen, E.K. Williamson, F.J. Stevens, and Y. Argon. 2000. Inhibition of amyloid fiber assembly by both BiP and its target peptide. Immunity, 13:433-442.
Dul, J.L., P. D. Davis, E.K. Williamson, F.J. Stevens and Y. Argon. 2001. Hsp70 and antifibrillogenic peptides promote degradation and inhibit intracellular aggregation of amyloidogenic light chains. J. Cell Biol., 152:705-715.
Gidalevitz, T., C. Biswas, H. Ding, D. Schneidman-Duhovny, H.J. Wolfson, F. Stevens, S. Radford and Y. Argon. 2004. Identification of the N-terminal peptide binding site of GRP94. J. Biol. Chem., 279:16543-16552.
Elkabetz, Y., Y. Argon and S. Bar-Nun. 2005. Cysteines in the CH1 domain underlie retention of unassembled Ig heavy chains. J. Biol. Chem., 280:14402-14412.
Biswas, C., U Sriram, B. Ciric, O. Ostrovsky, S. Gallucci and Y. Argon. 2006. The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional APCs. Int. Immunol., 18:1147-1157.
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