Synergistic effect between CD40 and class II signals overcome the requirement for class II dimerization in superantigen-induced cytokine gene expression
✍ Scribed by Khalil Mehindate; Reem Al-Daccak; Farida Damdoumi; Walid Mourad
- Book ID
- 102826288
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 653 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Synergistic effect between CD40 and class I1 signals overcome the requirement for class I1 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 I1 molecules, they differ in their mode of binding. Signaling induced by these toxins via MHC class I1 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 p or tumor necrosis factor-a gene expression. Treatment of THP-1 cells with interferon-y increased the level of MHC class I1 expression but did not enhance the SEB and TSST-1 response. However, crosslinking of SEB or TSST-1 bound to MHC class I1 molecules with specific antibodies leads to cytokine gene expression, indicating that dimerization of class I1 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 I1 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 I1 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.