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.
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 beta-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.
Langlois
Marc-André
MA
Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier de l'université Laval, Faculté de Médecine, Université Laval, Quebec G1V 4G2, Canada.
El Fakhry
Youssef
Y
Mourad
Walid
W
D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial; D001483:Base Sequence; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers; D019281:Dimerization; D006684:HLA-DR Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008934:Mitogens / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011506:Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018089:Superantigens / Q000737:chemistry / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D015032:Zinc / Q000378:metabolism*
D000941:Antigens; D000942:Antigens, Bacterial; D017931:DNA Primers; D006684:HLA-DR Antigens; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D011994:Recombinant Proteins; D018089:Superantigens; D015032:Zinc