Takei S, Arora Y K, Walker S M
Department of Pediatrics, Childrens Hospital, Los Angeles, California 90027.
J Clin Invest. 1993 Feb;91(2):602-7. doi: 10.1172/JCI116240.
Superantigens are products of bacteria with dual affinity for HLA-DR and the variable region of the beta chain of the T cell receptor, leading to the stimulation of large numbers of T cells. Because there is evidence for the involvement of superantigens in various disease conditions in which intravenous IgG (IVIgG) is used as therapy, the purpose of the present study was to determine if IVIgG contains antibodies inhibitory to T cell stimulation by the superantigens. ELISA and Western assays revealed high concentrations of antibodies in the pooled IgG against eight different staphylococcal toxin (Staph-toxin) superantigens. The IVIgG inhibited in vitro stimulation of human peripheral blood T cells by the Staph-toxins, but did not inhibit responses elicited by phytohemagglutinin or anti-CD3. Inhibition was mediated by Staph-toxin-specific antibodies as shown by affinity adsorption depletion studies. The antibodies functioned by inhibiting the binding and/or presentation of Staph-toxins by DR+ accessory cells. In conclusion, this report is the first to show that normal pooled IgG contains antibodies against a major group of the superantigens, the Staph-toxins, and that the antibodies can inhibit Staph-toxin-elicited T cell activation, suggesting a possible immunoregulatory role for the antibodies in vivo.
超抗原是细菌产生的产物,对HLA - DR和T细胞受体β链可变区具有双重亲和力,可导致大量T细胞被激活。由于有证据表明超抗原参与了各种使用静脉注射免疫球蛋白(IVIgG)进行治疗的疾病状况,本研究的目的是确定IVIgG是否含有抑制超抗原刺激T细胞的抗体。酶联免疫吸附测定(ELISA)和蛋白质免疫印迹法显示,混合IgG中针对八种不同葡萄球菌毒素(葡萄球菌毒素)超抗原的抗体浓度很高。IVIgG可抑制葡萄球菌毒素对人外周血T细胞的体外刺激,但不抑制植物血凝素或抗CD3引发的反应。亲和吸附去除研究表明,抑制作用是由葡萄球菌毒素特异性抗体介导的。这些抗体通过抑制DR +辅助细胞对葡萄球菌毒素的结合和/或呈递发挥作用。总之,本报告首次表明正常混合IgG含有针对主要超抗原组(葡萄球菌毒素)的抗体,并且这些抗体可抑制葡萄球菌毒素引发的T细胞活化,提示这些抗体在体内可能具有免疫调节作用。