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J. Biol. Chem., Vol. 278, Issue 25, 22309-22315, June 20, 2003

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Zinc-binding Sites in the N Terminus of Mycoplasma arthritidis-derived Mitogen Permit the Dimer Formation Required for High Affinity Binding to HLA-DR and for T Cell Activation^*

Marc-André Langlois , Youssef El Fakhry and Walid Mourad 

From the Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier de l'université Laval, Faculté de Médecine, Université Laval, Quebec G1V 4G2, Canada

Zinc-dependent superantigens can be divided into two subfamilies based on how they use zinc ions for interactions with major histocompatibility complex (MHC) class II molecules. Members of the first subfamily use zinc ions for interactions with histidine 81 on the -chain of MHC class II molecules, whereas members of the second subfamily use zinc ions for dimer formation. The zinc-binding motif is located in the C terminus of the molecule in both subfamilies. While our recent studies with Mycoplasma arthritidis-derived mitogen (MAM) have provided the first direct evidence demonstrating the binding to MHC class II molecules in a zinc-dependent manner, it still not known how zinc coordinates the interaction. Data presented here show that the zinc ion is mainly required to induce MAM/MAM dimer formation. Residues in the N terminus of MAM are involved in dimer formation and MHC class II binding, while histidine 14 and aspartic acid 31 of the MAM sequence are the major residues mediating MAM/MAM dimerization. Zinc-induced dimer formation is necessary for MAM binding, MHC class II-induced cell-cell adhesion, and efficient T cell activation. Together these results depict the unique mode of interaction of MAM in comparison with other superantigens.

Received for publication, January 24, 2003 , and in revised form, April 1, 2003.

^* This work was supported by grants (to W. M.) from the Canadian Arthritis Society, the Canadian Arthritis Network, and the Canadian Institutes of Health Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a doctoral studentship award from the Canadian Institutes of Health Research. Present address: Unité de Recherche en Génétique Humaine, Centre de Recherche du CHUL, Pavillon CHUQ, RC-9300, 2705 blvd. Laurier, Sainte-Foy, Quebec G1V 4G2, Canada.

Recipient of a scientist award from the Canadian Arthritis Society. To whom correspondence should be addressed: Centre de Recherche en Rhumatologie et Immunlogie, CHUL, 2705 blvd. Laurier, T1-49, Quebec, Canada. Tel.: 418-654-2772; Fax: 418-654-2765; E-mail: walid.mourad{at}crchul.ulaval.ca.

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				H. Li, Y. Zhao, Y. Guo, Z. Li, L. Eisele, and W. Mourad Zinc Induces Dimerization of the Class II Major Histocompatibility Complex Molecule That Leads to Cooperative Binding to a Superantigen J. Biol. Chem., March 2, 2007; 282(9): 5991 - 6000. [Abstract] [Full Text] [PDF]