SELECTIVE BINDING OF BACTERIAL TOXINS TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-EXPRESSING CELLS IS CONTROLLED BY INVARIANT CHAIN AND HLA-DM

Bacterial superantigens (Sr-fgs) bind to major histocompatibility comp lex (MHC) class II molecules and activate T cells in a V beta-restrict ed fashion. We recently identified subsets of HLA-DR1 molecules that s how selectivity for SAgs. Here, we extend these observations Sv showin g that different cell lineages demonstrate distinct SAg-binding specif icities although they: all express HLA-DR1. Indeed, If cells bind stap hylococcal enterotoxin A (SEA) and toxic shock syndrome toxin 1 (TSST- 1) with high affinity while staphylococcal enterotoxin B (SEE) binding is barely detectable, In contrast, DR1-transfected HeLa cells show ef ficient binding of SEE, but not of SEA or TSST-1. We investigated the class II maturation events required for efficient interaction with SAg s and found that the ability of cells to bind and present the toxins c an be drastically modulated by coexpression of the class II-associated invariant chain (Ii) and HLA-DM. SEA binding to DBI molecules require d coexpression of Ii, whereas TSST-1 binding was selectively enhanced by RI, Binding of SEE was affected by cell type-specific factors other than Ii or DM. The selectivity of SAgs for different MNC class II pop ulations was minimally affected by HLA-DR intrinsic polymorphism and c ould not be explained by binding to alternative sites on DR molecules, Our results indicate that SAgs are sensitive to structural heterogene ity in class II molecules, which is consequent to the differential reg ulation of expression of antigen processing cofactors. Therefore, me s peculate that Staphylococcus aureus have retained the ability to expre ss numerous SAgs in adaptation to the microheterogeneity displayed by MHC class II molecules and that this may relate to their ability to in fect different tissues.