Comparison of coligenoid formation by B subunits of porcine and human Escherichia coli heat-labile enterotoxins

A hybrid B subunit (coligenoid) of heat-labile enterotoxin could not be made from human heat-labile enterotoxin B subunit(LTh-B) and porcine LTp-B subunit(LTp-B). LTp-B monomer was able to form coligenoid by reassociation with homologous LTp-B monomer, but not with heterogeneous LTh-B monomer and vice versa. The dissociation of both coligenoids into monomers by SDS treatment occurred in a time-dependent manner, but the dissociation of LTh-B colligenoid was faster than that of LTp-B coligenoid. The association of LTp-B monomer is tighter than that of LTh-B monomer. The pI values of LTp-B coligenoid, LTp-B monomer and denatured LTp-B monomer were similar at 9.6-9.8, while the pI values of LTh-B coligenoid, LTh-B monomer and denatured LTh-B monomer were determined as 5.6-5.8, 9.2-9.6 and 9.2-9.6, respectively. All the ionic amino acids of LTp-B exist on the coligenoid surface. The difference in pI values between LTh-B coligenoid and LTh-B monomer suggests that some basic amino acids are located within the LTh-B coligenoid complex, but are exposed in the LTh-B monomer. These data suggest that the 4 amino acid substitutions between LTh-B and LTp-B result in a three dimensional structure difference and a less stable formation of LTh-B coligenoid compared to LTp-B coligenoid.     

超级抗原在肿瘤免疫治疗中的应用

超级抗原（Superantigen,SAg）作为一种优秀的免疫激活剂,通过诱导T细胞的活化来增强机体抗肿瘤免疫反应,可能是未来肿瘤免疫治疗的新希望。“超级抗原”一词在1989年被首次提出,用来描述细菌毒素对免疫系统的高效刺激特性。金黄色葡萄球菌能产生约20种不同类型的金黄色葡萄球菌肠毒素（Staphylococcal enterotoxins,SEs),这类蛋白质抗原是典型的细菌超级抗原,是一种能够在极低浓度下即可有效刺激细胞毒性T淋巴细胞活性和促进细胞因子产生的诱导剂。超级抗原通过与抗原呈递细胞（APCs）上的主要组织相容性复合体II（MHC-II）的外沟和T细胞受体（Tcr）的特异性Vβ区交叉结合,直接激活T淋巴细胞,使含有TCR Vβ结构域的T细胞进行超表达,使免疫细胞释放大量的抗肿瘤细胞因子和其他效应分子。基于免疫细胞具有识别自我和非我的特点,超级抗原利用人体自身免疫系统杀死肿瘤细胞,因此在肿瘤免疫治疗领域具有巨大应用潜力。对超级抗原的生物活性特征、临床抗肿瘤效果、药物开发策略等多方面进行简要综述,并对其未来应用前景加以展望。对超级抗原的作用机理及临床应用的深入研究,将有助于肿瘤免疫治疗的发展,从而使通过T淋巴细胞干预治疗恶性肿瘤成为可能。