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抗体及辅助性T细胞对同源骨髓瘤蛋白W3129及其亚基反应的特异性

Specificity of antibody and helper T-cell responses to the isologous myeloma protein W3129 and its subunits.

作者信息

Bogen B, Hannestad K

出版信息

Mol Immunol. 1984 Jul;21(7):653-61. doi: 10.1016/0161-5890(84)90051-8.

Abstract

The specificity of BALB/c antibodies and Th elicited by BALB/c myeloma protein W3129 (alpha, kappa) and its subunits was studied. Antibodies were detected with RIA and ELISA techniques. Th were demonstrated by their ability to augment a secondary anti-NIP antibody response in a Mitchison type assay of adoptive immunity. The major proportion of antibodies elicited by the complete W3129 was directed to an idiotypic determinant(s) that depended on assembled H + L chains. The determinant(s) was probably located in or near the antibody combining site because binding was hapten-inhibitable. A second minor antibody population bound an idiotypic determinant(s) on VW3129H expressed on isolated H-chain as well as on the complete myeloma protein. A third and very weakly reactive set of antibodies was specific for a C alpha antigenic site(s) which was expressed much more efficiently on free than on assembled alpha-chains. The antibody response to free kappa W3129 was directed to idiotypic determinants that were inaccessible in the complete molecule. By contrast, free kappa W3129 elicited Th that responded to an idiotypic determinant(s) on VW3129K; the determinant(s) was expressed on both the isolated chain and the complete W3129, suggesting that Th responded to an idiotope not recognized by B-cells. Priming with free alpha W3129 failed in four out of five experiments to induce Th that responded to the complete W3129, demonstrating that a major difference existed between VH and VL of W3129 regarding their immunogenicity for Th. Nevertheless, free alpha W3129 did elicit antibody responses that displayed high reactivity with the complete molecule, indicating that certain serologically defined antigenic sites on the surface of W3129 are also expressed on isolated alpha W3129. Thus, certain differences were detected as to the specificities of Th and B-cells for W3129 and its subunits since they recognized separate idiotopes located in the VL- or VH-region, respectively. The pattern of Th recognition of W3129 resembled that of another isologous myeloma protein, M315, but was unlike that of a third, J558, previously described from this laboratory.

摘要

研究了BALB/c骨髓瘤蛋白W3129(α,κ)及其亚基引发的BALB/c抗体和Th细胞的特异性。采用放射免疫分析(RIA)和酶联免疫吸附测定(ELISA)技术检测抗体。通过在米切森型过继免疫试验中增强二次抗NIP抗体反应的能力来证明Th细胞。由完整的W3129引发的抗体的主要部分针对取决于组装的重链(H)和轻链(L)的独特型决定簇。该决定簇可能位于抗体结合位点内或附近,因为结合是可被半抗原抑制的。第二小部分抗体结合在分离的重链以及完整的骨髓瘤蛋白上表达的VW3129H上的一个独特型决定簇。第三组反应非常弱的抗体对一个Cα抗原位点具有特异性,该位点在游离α链上的表达效率远高于组装的α链。对游离κW3129的抗体反应针对完整分子中无法接近的独特型决定簇。相比之下,游离κW3129引发的Th细胞对VW3129K上的一个独特型决定簇有反应;该决定簇在分离的链和完整的W3129上均有表达,表明Th细胞对一个B细胞未识别的独特位有反应。在五分之四的实验中,用游离αW3129进行预刺激未能诱导出对完整W3129有反应的Th细胞,这表明W3129的重链可变区(VH)和轻链可变区(VL)在对Th细胞的免疫原性方面存在重大差异。然而,游离αW3129确实引发了与完整分子具有高反应性的抗体反应,表明W3129表面某些血清学定义的抗原位点在分离的αW3129上也有表达。因此,检测到Th细胞和B细胞对W3129及其亚基的特异性存在某些差异,因为它们分别识别位于轻链可变区或重链可变区的不同独特位。W3129的Th细胞识别模式类似于另一种同种骨髓瘤蛋白M315,但与本实验室先前描述的第三种骨髓瘤蛋白J558不同。

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