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SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Ig\u03ba and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human-mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production.<\/jats:p>","DOI":"10.1128\/iai.01121-09","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T02:24:18Z","timestamp":1269311058000},"page":"2801-2811","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies"],"prefix":"10.1128","volume":"78","author":[{"given":"Mulualem E.","family":"Tilahun","sequence":"first","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"},{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Govindarajan","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nalini","family":"Shah-Mahoney","sequence":"additional","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca G.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashenafi Y.","family":"Tilahun","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kannan","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Margulies","sequence":"additional","affiliation":[{"name":"Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David I.","family":"Ratner","sequence":"additional","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara A.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Goldsby","sequence":"additional","affiliation":[{"name":"Department of Biology, Amherst College, Amherst, Massachusetts 01002"},{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2003.11.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1189\/jlb.69.6.921","volume":"69","year":"2001","unstructured":"Arad, G., D. 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