Identification and characterization of novel superantigens from Streptococcus pyogenes.
Identification and characterization of novel superantigens from Streptococcus pyogenes.
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DOI：
10.1084/jem.189.1.89
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发表时间：
1999-01-04
影响因子：
15.3
通讯作者：
Fraser, J D
中科院分区：
文献类型：
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作者：
Proft, T;Moffatt, S L;Berkahn, C J;Fraser, J D
从俄克拉荷马州大学的化脓性链球菌M1基因组数据库中鉴定出三种新的链球菌超抗原基因（spe-g、spe-h和spe-j）。第四个新基因（smez-2）是从S.化脓性链球菌菌株2035，基于与链球菌促有丝分裂外毒素Z（SMEZ）基因的序列同源性。SMEZ-2、SPE-G和SPE-J与SMEZ和链球菌致热原外毒素（SPE）-C最密切相关，而SPE-H与葡萄球菌毒素的相似性高于与任何其他链球菌毒素的相似性。重组（r）SMEZ、rSMEZ-2、rSPE-G和rSPE-H对人外周血淋巴细胞具有促有丝分裂作用，半数最大反应为0.02 - 50 pg/ml（分别为rSMEZ-2和rSPE-H）。SMEZ-2是迄今为止发现的最有效的超抗原（SAg）。除rSPE-G外，所有毒素对鼠T细胞均具有活性，但效力降低。与人B-淋巴母细胞系的结合显示为锌依赖性的，具有15-65 nM的高结合亲和力。来自模拟蛋白质结构和竞争性结合实验的证据表明，每种毒素与主要组织相容性复合体II类β链的高亲和力结合。毒素之间的结合竞争是不同的，并显示重叠，但离散的结合的第二类分子的亚组的层次顺序（SMEZ，SPE-C）> SMEZ-2 > SPE-H > SPE-G。新型SAg最常见的靶点是表达人Vβ2.1和Vβ4的T细胞。这可能反映了该Vβ亚群在革兰氏阳性菌的免疫防御中的特定作用。
Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma. A fourth novel gene (smez-2) was isolated from the S. pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene. SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin. Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively). SMEZ-2 is the most potent superantigen (SAg) discovered thus far. All toxins, except rSPE-G, were active on murine T cells, but with reduced potency. Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15–65 nM. Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II β chain. Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G. The most common targets for the novel SAgs were human Vβ2.1- and Vβ4-expressing T cells. This might reflect a specific role for this subset of Vβs in the immune defense of gram-positive bacteria.