Binding of Mycoplasma arthritidis-derived mitogen to human MHC class II molecules via its N terminus is modulated by invariant chain expression and its C terminus is required for T cell activation.
Mycoplasma arthritidis-derived mitogen (MAM) is considered to be a member of the super-antigen family despite the fact that there is no evidence until now indicating its binding to MHC class II molecules. To demonstrate its direct binding and to determine the regions involved in MHC class II and TCR interactions, we generated a recombinant wild-type and two truncated forms of the MAM protein. Data obtained in the course of the present investigation show that MAM binds specifically and significantly to human MHC class II molecules. Evidence is also provided that MAM bears two distinct binding regions: one is located within its N terminus and interacts with MHC class II molecules, while the second region which is located in its C terminus mediates its recognition by the TCR. Association of the MHC class II-associated invariant chain peptide with the peptide binding groove on the cell surface completely abolished MAM binding and presentation. This inhibitory effect is restored by the expression of HLA-DM molecules, suggesting that the nature of the peptide within the binding groove and/or the stability of the MHC class II molecules on the cell surface may modulate MAM/MHC class II interactions.
Langlois
M A
MA
Centre de Recherche en Rhumatologie et Immunologie, CHUQ and Laval University, Ste-Foy, Canada.
Etongué-Mayer
P
P
Ouellette
M
M
Mourad
W
W
D000941:Antigens; D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001665:Binding Sites; D002461:Cell Line, Transformed; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008934:Mitogens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D009174:Mycoplasma / Q000276:immunology*; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D018089:Superantigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000942:Antigens, Bacterial; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C045084:invariant chain