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Bianca Conti-Fine, Ph.D. Professor, Department of Biochemistry, Molecular Biology and Biophysics E-mail: conti1@molbio.cbs.umn.edu

Research Interests:

Myasthenia Gravis (MG) is a human paralysis due to an autoimmune response against the muscle nicotinic receptor (AcChoR) with thymus (T)-dependent production of antibodies. The AcChoR structure is well known. In our lab we clone from human blood both the helper T-cell and the antibody-producing B-cells which collaborate in the production of anti-AcChoR antibodies. The segments of the human AcChoR which seem to contain antigenic determinants recognized by either the T- or B-cell lines have been identified and synthesized. This therefore offers the unique opportunity to study at the molecular level how the human immune system perceives a complex antigen as a tridimensional object, and which parts of the AcChoR molecule are recognized by the different compartments of the immune system that cooperate in the production of the anti-AcChoR autoantibodies. In addition, comparison of the sets of the determinants recognized by each patient with his or her MHC haplotype will give indications as to whether the MHC products, and in particular the class II molecules, determine the recognition of particular areas of the AcChoR molecule. Answering these questions will be an important step forward both for understanding the pathogenesis of MG and for a rational approach to its treatment.

We have carried out similar studies in the mouse model of MG (Experimental Autoimmune MG, EAMG), obtained by immunizing mice of different inbred strains with purified AcChoR. The results of those studies are presently being used to develop specific immunosuppressive treatments of EAMG, which, based on the results of the studies summarized above, could be used in the near future for the treatment of MG patients.

A third interest of our group is the elucidation of the tridimensional structure of the AcChoR, with particular emphasis on the fine structure of two surface domains important for the function and the autoimmune pathology of this receptor, namely, the binding site for cholinergic ligands and the Main Immunogenic Region--a small area on the muscle AcChoR surface which dominated the autoantibody response in both MG and EAMG.

Selected Publications:

Wang W, Milani M, Ostlie N, Okita D, Agarwal RK, Caspi R, Conti-Fine BM. C57BL/6 mice genetically deficient in IL-12/IL-23 and IFN-gamma are susceptible to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non-Th1 cells. J Immunol. 2007 Jun 1;178(11):7072-80.

Hu G, Guo D, Key NS, Conti-Fine BM. Cytokine production by CD4+ T cells specific for coagulation factor VIII in healthy subjects and haemophilia A patients. Thromb Haemost. 2007 May;97(5):788-94.

Conti-Fine BM, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin Invest. 2006 Nov;116(11):2843-54.

Milani M, Ostlie N, Wu H, Wang W, Conti-Fine BM. CD4+ T and B cells cooperate in the immunoregulation of Experimental Autoimmune Myasthenia Gravis. J Neuroimmunol. 2006 Oct;179(1-2):152-62.

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