Synergistic effect between CD40 and class II signals overcome the requirement for class II dimerization in superantigen-induced cytokine gene expression.
Although staphylococcal enterotoxin A (SEA), B (SEB), and toxic shock syndrome toxin 1 (TSST-1) bind to major histocompatibility complex (MHC) class II molecules, they differ in their mode of binding. Signaling induced by these toxins via MHC class II molecules seems to be largely mediated by their mode of interaction. In the present study, we have demonstrated that contrary to SEA, stimulation of the human monocytic cell line THP-1 with SEB or TSST-1 failed to induce interleukin-1 beta or tumor necrosis factor-alpha gene expression. Treatment of THP-1 cells with interferon-gamma increased the level of MHC class II expression but did not enhance the SEB and TSST-1 response. However, cross-linking of SEB or TSST-1 bound to MHC class II molecules with specific antibodies leads to cytokine gene expression, indicating that dimerization of class II molecules is a requirement for this superantigen-induced response. The presence of anti-CD40 antibodies in the course of SEB or TSST-1 stimulation overcomes this requirement, indicating that certain signal(s) induced via CD40 molecules can replace those induced by dimerization of class II molecules. Pretreatment with anti-lymphocyte functional antigen-1 (LFA-1) antibodies completely inhibited SEA-induced response as well as that induced by SEB or TSST-1 in the presence of CD40 antibodies, supporting the involvement of LFA-1 intercellular adhesion molecule system in these responses. The entirety of these results demonstrate clearly that dimerization of class II molecules is a prerequisite for superantigen-induced T cell-independent cytokine gene expression which can be replaced by signaling via CD40 in an LFA-1-dependent system.
Mehindate
K
K
Centre de recherche en Rhumatologie Immunologie, Centre Hospitalier de l'Université Laval, Sainte-Foy, Canada.
al-Daccak
R
R
Damdoumi
F
F
Mourad
W
W
D001427:Bacterial Toxins; D019013:CD40 Antigens / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D018089:Superantigens / Q000494:pharmacology*
D001427:Bacterial Toxins; D019013:CD40 Antigens; D016207:Cytokines; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal