Functional analysis of Mycoplasma arthritidis-derived mitogen interactions with class II molecules.
The ability of superantigens (SAGs) to trigger various cellular events via major histocompatibility complex (MHC) class II molecules is largely mediated by their mode of interaction. Having two MHC class II binding sites, staphylococcal enterotoxin A (SEA) is able to dimerize MHC class II molecules on the cell surface and consequently induces cytokine gene expression in human monocytes. In contrast, cross-linking with specific monoclonal antibodies or T-cell receptor is required for staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSST-1) to induce similar responses. In the present study, we report how Mycoplasma arthritidis-derived mitogen (MAM) may interact with MHC class II molecules to induce cytokine gene expression in human monocytes. The data presented indicate that MAM-induced cytokine gene expression in human monocytes is Zn2+ dependent. The MAM-induced response is completely abolished by pretreatment with SEA mutants that have lost their capacity to bind either the MHC class II alpha or beta chain, with wild-type SEB, or with wild-type TSST-1, suggesting that MAM induces cytokine gene expression most probably by inducing dimerization of class II molecules. In addition, it seems that SEA and MAM interact with the same or overlapping binding sites on the MHC class II beta chain and, on the other hand, that they bind to the alpha chain most probably through the regions that are involved in SEB and TSST-1 binding.
Bernatchez
C
C
Centre de Recherche en Rheumatologie Immunologie, Centre Hospitalier de l'Université Laval, Sainte-Foy, Québec, Canada.
Al-Daccak
R
R
Mayer
P E
PE
Mehindate
K
K
Rink
L
L
Mecheri
S
S
Mourad
W
W
D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial; D002460:Cell Line; D019281:Dimerization; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000502:physiology*; D009174:Mycoplasma / Q000276:immunology*; D011506:Proteins; D018089:Superantigens / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
D000941:Antigens; D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D018089:Superantigens; D015032:Zinc