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 larg ely mediated by their mode of interaction. Having two MHC class II bin ding sites, staphylococcal enterotoxin A (SEA) is able to dimerize MRC class II molecules on the cell surface and consequently induces cytok ine gene expression in human monocytes. In contrast, cross-linking wit h specific monoclonal antibodies or T-cell receptor is required for st aphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1 (TSS T-1) to induct similar responses, In the present study, we report how Mycoplasma arthritidis derived mitogen (MAM) may interact with MHC cla ss 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 com pletely abolished by pretreatment with SEA mutants that have lost thei r capacity to bind either the MRC class II alpha or beta chain, with w ild-type SEB, or with wild-type TSST-1, suggesting that MAM induces cy tokine gene expression most probably by inducing dimerization of class II molecules, In addition, it seems that SEA and MAM interact with th e 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 t hrough the regions that are involved in SEB and TSST-1 binding.