Antibody conjugates mimic specific B cell presentation of antigen: relationship between T and B cell specificity.
Antibody conjugates mimic specific B cell presentation of antigen: relationship between T and B cell specificity.
复制标题
抗体偶联物模拟抗原的特异性 B 细胞呈递：T 细胞和 B 细胞特异性之间的关系。
DOI：
10.4049/jimmunol.138.12.4133
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发表时间：
1987
影响因子：
4.4
通讯作者：
J. Berzofsky
中科院分区：
文献类型：
--
作者：
S. Ozaki;J. Berzofsky
我们通过共价偶联抗小鼠μ链的抗体和抗标称抗原肌红蛋白的单克隆抗体开发了抗体缀合物，作为抗原呈递的工具和作为抗原特异性B细胞和T-B相互作用的抗原特异性呈递的模型。在抗体缀合物的存在下，肌红蛋白特异性Iad限制性克隆T细胞在比没有缀合物的刺激浓度低1000倍的肌红蛋白浓度下增殖。只有当Iad脾细胞被1000 R照射而不是3300 R照射时才观察到这种增强的呈递，这与B细胞呈递一致。偶联物各组分的简单混合物没有增强作用。在用于抗原呈递的浓度下，缀合物本身对脾B细胞或克隆的T细胞都没有促有丝分裂作用。缀合物减少了最大反应所需的抗原呈递细胞的数量，但不改变反应的动力学。缀合物的增强提呈需要与B细胞的遗传限制性相互作用。通过使用具有不同抗原特异性的各种T细胞克隆或系以及用已知表位特异性的单克隆抗体构建的不同缀合物来证实增强的呈递的抗原特异性。增强的呈递被与外源性小鼠IgM或抗小鼠μ链的竞争显著抑制，但不被针对Fc受体的单克隆抗体显著抑制。因此，缀合物包被的B细胞用作肌红蛋白特异性B细胞的模型，因为它们可以以极低的浓度摄取特异性抗原并可以将抗原呈递给特异性T细胞。该模型系统可以应用于任何抗原和任何物种，而不需要开发抗原特异性B细胞克隆，这对于大多数抗原和实验动物物种尚不可能。该系统使我们能够研究T细胞表位和B细胞表位之间的关系，当这些细胞以抗原特异性和Ia限制性方式相互作用时。使用抗肌红蛋白的不同单克隆抗体和已知抗原特异性的各种肌红蛋白特异性克隆T细胞的抗体缀合物的实验显示，存在一些特定的组合，其中观察到更有限的抗原呈递增强。（400字处截断摘要）
We developed antibody conjugates by covalently coupling antibodies against mouse mu-chain and monoclonal antibodies against nominal antigen, myoglobin, as a tool for antigen presentation and as a model of specific presentation of antigen by antigen-specific B cells and T-B interaction. In the presence of the antibody conjugates, myoglobin-specific Iad-restricted cloned T cells proliferated at 1000-fold lower concentration of myoglobin than the stimulatory concentration without the conjugates. This enhanced presentation was observed only when Iad spleen cells were 1000 R-irradiated but not 3300 R-irradiated, consistent with B cell presentation. The simple mixture of each component of the conjugates had no enhancement effects. The conjugates per se had no mitogenic effects on either splenic B cells or the cloned T cells at concentrations employed for antigen presentation. The conjugates reduced the number of antigen-presenting cells required for the maximal response but did not change the kinetics of response. The enhanced presentation by the conjugates required a genetically restricted interaction with B cells. Antigen specificity of the enhanced presentation was confirmed by using various T cell clones or lines with different antigen specificities and different conjugates constructed with monoclonal antibodies of known epitope specificity. The enhanced presentation was significantly inhibited by competition with exogenous mouse IgM or anti-mouse mu-chain but was not significantly inhibited by monoclonal antibodies against Fc receptor. Thus, conjugate-coated B cells serve as models for myoglobin-specific B cells in that they can take up specific antigens at extremely low concentration and can present the antigen to specific T cells. This model system can be applied to any antigen and any species without the need to develop antigen-specific B cell clones, which is not yet possible for most antigens and species of experimental animals. This system allowed us to investigate the relationship between T cell epitope and B cell epitope when these cells interact with each other in an antigen-specific and Ia-restricted manner. Experiments using antibody conjugates of different monoclonal antibodies against myoglobin and various myoglobin-specific cloned T cells of known antigen specificity revealed that there are some particular combinations in which much more limited enhancement of antigen presentation is observed.(ABSTRACT TRUNCATED AT 400 WORDS)