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In the present study, we have demonstrated that contrary to SEA, stimulation of the human monocytic cell line THP\u20101 with SEB or TSST\u20101 failed to induce interleukin\u20101\u03b2 or tumor necrosis factor\u2010\u03b1 gene expression. Treatment of THP\u20101 cells with interferon\u2010\u03b3 increased the level of MHC class II expression but did not enhance the SEB and TSST\u20101 response. However, cross\u2010linking of SEB or TSST\u20101 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\u2010induced response. The presence of anti\u2010CD40 antibodies in the course of SEB or TSST\u20101 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\u2010lymphocyte functional antigen\u20101 (LFA\u20101) antibodies completely inhibited SEA\u2010induced response as well as that induced by SEB or TSST\u20101 in the presence of CD40 antibodies, supporting the involvement of LFA\u20101 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\u2010induced T cell\u2010independent cytokine gene expression which can be replaced by signaling via CD40 in an LFA\u20101\u2010dependent system.<\/jats:p>","DOI":"10.1002\/eji.1830260917","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T02:34:16Z","timestamp":1172802856000},"page":"2075-2080","source":"Crossref","is-referenced-by-count":20,"title":["Synergistic effect between CD40 and class II signals overcome the requirement for class II dimerization in superantigen\u2010induced cytokine gene expression"],"prefix":"10.1002","volume":"26","author":[{"given":"Khalil","family":"Mehindate","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem","family":"Al\u2010Daccak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farida","family":"Damdoumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walid","family":"Mourad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.000533"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.11.4210"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/339221a0"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2658055"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2185544"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.4049\/jimmunol.147.11.3876","volume":"147","author":"Chintagumpala M. 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