Poon R Y, Kapp J A, Pierce C W, Sorensen C M
J Immunol. 1986 Dec 15;137(12):3709-16.
We have previously identified and described two distinct types of suppressor T cell factors specific for the PFC response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) or L-glutamic acid50-L-tyrosine50 (GT). Both of these factors are antigen-specific and I-J+. GAT-TsF1 is not MHC-restricted and is composed of a single polypeptide chain, whereas GAT-TsF2 is MHC-restricted and is composed of two different polypeptide chains. We have not previously found evidence for an obligatory, idiotype-specific suppressor T cell in this suppressor pathway. However, we now report that idiotype-specific suppressor T cells can be elicited by exposing normal spleen cells to GAT-TsF1 or GAT-TsF2 in the absence of antigen in vitro. These factor (TsF1/TsF2)-induced cells have been fused with the AKR thymoma, BW5147, and hybridomas were selected for production of suppressor factors that inhibit GAT-specific antibody responses in vitro. In this report, we characterize one monoclonal factor from each fusion. Neither factor binds GAT or the related co-polymer, GT; both factors have binding sites for GAT-specific idiotypes but not for unrelated idiotypes either in the form of antibody immobilized on Sepharose or as cell surface determinants expressed by B cell hybridomas. Moreover, their reactivities for a panel of monoclonal anti-GAT antibodies are overlapping but not identical. Both factors are composed of two polypeptide chains, and both chains are required for suppressive activity; one chain bears the I-J determinant, whereas the other possesses the idiotype-binding activity of the intact molecule. Both idiotype-binding factors are restricted by MHC- and Igh-linked genes, and transcomplementation is observed in the F1 mice between MHC-congenic and Igh-congenic parents. Both factors are active late in Mishell-Dutton cultures. These data support the contention that these two factors are similar but nonidentical members of an anti-idiotypic class of GAT-specific suppressor factors.
我们先前已鉴定并描述了两种不同类型的抑制性T细胞因子，它们对L-谷氨酸60-L-丙氨酸30-L-酪氨酸10（GAT）或L-谷氨酸50-L-酪氨酸50（GT）的PFC反应具有特异性。这两种因子均具有抗原特异性且为I-J+。GAT-TsF1不受MHC限制，由一条单一多肽链组成，而GAT-TsF2受MHC限制，由两条不同的多肽链组成。我们之前在该抑制途径中未发现存在必需的、独特型特异性抑制性T细胞的证据。然而，我们现在报告，在体外无抗原的情况下，将正常脾细胞暴露于GAT-TsF1或GAT-TsF2可诱导出独特型特异性抑制性T细胞。这些由因子（TsF1/TsF2）诱导的细胞已与AKR胸腺瘤BW5147融合，并筛选出杂交瘤以产生在体外抑制GAT特异性抗体反应的抑制因子。在本报告中，我们对每次融合产生的一种单克隆因子进行了表征。两种因子均不结合GAT或相关共聚物GT；两种因子均具有针对GAT特异性独特型的结合位点，但对于固定在琼脂糖上的抗体形式或B细胞杂交瘤表达的细胞表面决定簇形式的无关独特型均无结合位点。此外，它们对一组单克隆抗GAT抗体的反应性有重叠但不完全相同。两种因子均由两条多肽链组成，且两条链对于抑制活性均是必需的；一条链带有I-J决定簇，而另一条链具有完整分子的独特型结合活性。两种独特型结合因子均受MHC和Igh连锁基因的限制，并且在F1小鼠的MHC同基因和Igh同基因亲本之间观察到反式互补。两种因子在米舍尔-达顿培养后期均具有活性。这些数据支持了这样的论点，即这两种因子是GAT特异性抑制因子的抗独特型类别中相似但不相同的成员。
