BINDING OF TOXIC SHOCK SYNDROME TOXIN-1 TO MURINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES
BINDING OF TOXIC SHOCK SYNDROME TOXIN-1 TO MURINE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES
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DOI：
10.1002/eji.1830200907
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发表时间：
1990-09-01
影响因子：
5.4
通讯作者：
GEHA, RS
中科院分区：
文献类型：
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作者：
SCHOLL, PR;SEKALY, RP;GEHA, RS
葡萄球菌外毒素中毒性休克综合征毒素-1(TSST-1)对小鼠和人淋巴细胞有很强的刺激作用。这是TSST-1与主要组织相容性复合体(MHC)II类分子结合的结果，以及TSST-1-MHC II类复合体以V.beta限制性的方式与T细胞受体结合的结果。通过放射学和功能分析，我们最近发现TSST-1可以与所测试的所有HLA-DR(n=14)、HL A-DQ(n=2)和HLA-DP(n=2)表型结合。在这项研究中，我们检测了小鼠MHC II类分子与TSST-1结合的能力。TSST-1可与BALB-c(H-2d)和C57BL/6(H-2b)细胞特异性高亲和力结合，但不能与C3H(H-2k)脾细胞结合。Scatchard分析估计的该结合的Kd与TSSt-1与HLA-DR结合的Kd在相同的纳摩尔范围内。~(125)I标记的TSST-1与BALB/c来源的B细胞淋巴瘤细胞和L细胞的结合与I-A分子的表达有关，而与I-E分子的表达无关。此外，I-A+、I-E-细胞能够支持TSST-1诱导的T细胞增殖，而I-A-、I-E+细胞则不能。TSST-1与I-AK的结合亲和力似乎远低于I-Ad。表达杂合DR.α：I-Eβk分子的L细胞，而不表达I-Eαk：DR1β分子的细胞。可与TSST-1结合，有效支持TSST-1诱导的T细胞增殖。这表明高度同源的I-Eα之间的微小差异。和阿尔法博士。链是决定MHC II类分子与TSST-1亲和力的关键。这些结果表明，与人类相比，小鼠的TSST-1与MHC II类分子的结合受到表型的强烈影响。对这些差异的分子基础的分析可能有助于定位MHC II类分子上的葡萄球菌外毒素结合部位。
The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST-1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a V.beta.-restricted fashion of the T cell receptor by the TSST-1-MHC class II complex. Using radiologand and functional assays we have recently shown that TSST-1 binds to all HLA-DR (n = 14), HLA-DQ (n = 2) and HLA-DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST-1. Specific high-affinity binding of TSST-1 was detectable to unfractionated BALB-c (H-2d) and C57BL/6 (H-2b) but not to C3H (H-2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSSt-1 to HLA-DR. Binding of 125I-labeled TSST-1 to BALB/c-derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I-A molecules, but not with the expression of I-E molecules. Furthermore, I-A+, I-E- cells but not I-A-, I-E+ cells were able to support TSST-1-induced T cell proliferation. The binding affinity of TSST-1 for I-Ak appears to be much lower than for I-Ad. L cell transfectants expressing hybrid DR.alpha.: I-E.beta.k molecules, but not those expressing I-E.alpha.k: DR1.beta. molecules, could bind TSST-1 and efficiently support TSST-1 induced T cell proliferation. This suggests that minor differences in the highly homologous I-E.alpha. and DR.alpha. chains are critical in determining the affinity of the MHC class II molecule for TSST-1. These results demonstrate that the binding of TSST-1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules.