Karasuyama H, Kim M, Okumura K, Tada T
Eur J Immunol. 1984 May;14(5):413-20. doi: 10.1002/eji.1830140506.
Hybridomas producing monoclonal antibodies (mAb) specific for immunoglobulin heavy chain (Igh) allotype-linked gene products expressed only on functional T cells but not on B cells and macrophages were established by fusion of allotype congenic SJL (Igh-1b) and SJA /9 (Igh-1a) B cells immunized reciprocally with partner spleen cells with a myeloma P3-X63-Ag8-653 of BALB/c origin. Nine mAb have been selected on the criteria that they can specifically block various antigen-dependent functions of known T cell subsets in in vitro immune responses of mouse strains having the corresponding Igh allotype, but not the other one. These included (a) four mAb that augment the in vitro secondary antibody response of either Igh-1a or Igh-1b strains and thus are considered to react with the Igh-linked allotypic determinant expressed on suppressor T cells, (b) one mAb that inhibits the helper T cell activity of Igh-1b but not of Igh-1a strains, (c) two mAb that inhibit the antigen-induced proliferative response of Igh-1a but not Igh-1b strains, and (d) two mAb that block the cytotoxicity of alloreactive cytotoxic T cells of Igh-1a strains. The linkage to Igh-1 allotype of the T cell products was established by testing with Igh-1-congenic strains with different backgrounds including the H-2 complex. Some of the mAb were able to react with cloned hybridomas and a continuous cell line of the given allotype and functions. Each mAb was able to block one of the known functions of T cell subsets, but not others, indicating the existence of the heterogeneity and multiplicity of the Igh allotype-linked products on T cells.
通过将同种异型近交系SJL(Igh-1b)和SJA/9(Igh-1a)B细胞与BALB/c来源的骨髓瘤P3-X63-Ag8-653分别用对方脾细胞进行免疫后相互融合,建立了产生单克隆抗体(mAb)的杂交瘤,这些单克隆抗体特异性针对仅在功能性T细胞而非B细胞和巨噬细胞上表达的免疫球蛋白重链(Igh)同种型连锁基因产物。根据它们能够特异性阻断具有相应Igh同种型的小鼠品系体外免疫反应中已知T细胞亚群的各种抗原依赖性功能,但不能阻断另一种品系的功能这一标准,筛选出了9种单克隆抗体。其中包括:(a)4种单克隆抗体可增强Igh-1a或Igh-1b品系的体外二次抗体反应,因此被认为与抑制性T细胞上表达的Igh连锁同种异型决定簇发生反应;(b)1种单克隆抗体抑制Igh-1b品系的辅助性T细胞活性,但不抑制Igh-1a品系的;(c)2种单克隆抗体抑制Igh-1a品系而非Igh-1b品系的抗原诱导增殖反应;(d)2种单克隆抗体阻断Igh-1a品系的同种异体反应性细胞毒性T细胞的细胞毒性。通过用包括H-2复合体在内的不同背景的Igh-1近交系进行测试,确定了T细胞产物与Igh-1同种型的连锁关系。一些单克隆抗体能够与给定同种型和功能的克隆杂交瘤及连续细胞系发生反应。每种单克隆抗体都能够阻断T细胞亚群的一种已知功能,但不能阻断其他功能,这表明T细胞上Igh同种型连锁产物存在异质性和多样性。