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一种杂交瘤衍生的T细胞因子的特性,该因子可促进携带显性交叉反应独特型抗体的产生。

Characterization of a hybridoma-derived T cell factor that promotes the production of antibodies bearing a dominant cross-reactive idiotype(s).

作者信息

Wardzala A M, Bowen M B, Jendrisak G S, Bellone C J

机构信息

Department of Microbiology, St. Louis University School of Medicine, MO 63104.

出版信息

J Mol Cell Immunol. 1986;2(5):243-53.

PMID:2978231
Abstract

The participation of postulated subsets of T helper cells in antigen-specific antibody responses has generated both interest and controversy among immunologists. Specifically the import as well as the very existence of multiple populations of T helper cells has led to an intense search in recent years for cloned lines of such subsets that permit unambiguous classification and study. Furthermore, the means by which some of these T cells induce antibody responses may be via the elaboration of soluble factors mandating their characterization both biochemically and mechanistically. We have recently reported the existence of a T helper factor present in a 24-h Con A supernatant that specifically enhances an idiotype-bearing (Id+) response to trinitrophenol (TNP). The unique biochemical properties of this substance, namely, its capacity to bind both antigen and cross-reactive idiotype (CRI), has led to the generation of a cloned T cell hybridoma that constitutively "secretes" a factor which appears identical to the helper activity in Con A Sn. The cloned T cell hybridoma, herein designated LOP 1.4, elaborates a factor which selectively enhances the CRI+ anti-TNP antibody response in vitro. The specificity of the assay employed as well as its sensitivity for detecting significant enhancement of the percent CRI+ anti-TNP PFC response lent itself well as a useful vehicle for subsequent characterization of the factor. The LOP 1.4 factor, which can act at the later stages of the B cell response in a dose-dependent fashion, was characterized by affinity chromatography in order to probe the mechanism of its selective Id enhancement. The factor binds both the idiotype and the ligand for which one of the idiotype-bearing monoclonal antibodies is specific. That the factor binds idiotype and can be eluted selectively with ligand but not with noncross-reacting ligand suggests that the factor possesses separate but not independent binding sites, or alternatively, a single binding site that preferentially binds to a unique composite of antigen-idiotype. In addition, the factor bears I-J determinants, consistent with what we have previously detected on the surface of TH2-like cells. These results, collectively, suggest that the T cell hybridoma LOP 1.4 is a TH2-like cell (supporting the concept of multiple TH subsets) in light of its ability to enhance an idiotypic response to specific antigen through the production of a soluble factor that demonstrates affinity for both antigen and idiotype. In addition, like the I-J+ TH2 cell, the LOP 1.4 factor also bears I-J region determinants.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

假定的辅助性T细胞亚群参与抗原特异性抗体反应,这在免疫学家中引发了兴趣和争议。具体而言,多种辅助性T细胞群体的重要性及其存在本身,促使近年来人们对这类亚群的克隆系进行了深入研究,以便进行明确的分类和研究。此外,其中一些T细胞诱导抗体反应的方式可能是通过分泌可溶性因子,这就需要从生化和机制上对其进行表征。我们最近报道,在24小时刀豆蛋白A(Con A)上清液中存在一种辅助性T细胞因子,它能特异性增强针对三硝基苯酚(TNP)的携带独特型(Id +)反应。这种物质独特的生化特性,即它既能结合抗原又能结合交叉反应独特型(CRI),导致产生了一种克隆的T细胞杂交瘤,该杂交瘤组成性地“分泌”一种因子,这种因子似乎与Con A上清液中的辅助活性相同。在此命名为LOP 1.4的克隆T细胞杂交瘤分泌一种因子,该因子在体外能选择性增强CRI +抗TNP抗体反应。所采用检测方法的特异性及其检测CRI +抗TNP空斑形成细胞(PFC)反应显著增强的灵敏度,使其非常适合作为后续表征该因子的有效工具。LOP 1.4因子能以剂量依赖的方式作用于B细胞反应的后期,通过亲和层析对其进行表征,以探究其选择性独特型增强的机制。该因子能结合独特型以及一种携带独特型的单克隆抗体所特异性识别的配体。该因子能结合独特型,并且能用配体选择性洗脱,但不能用非交叉反应配体洗脱,这表明该因子具有独立但不相互独立的结合位点,或者说有一个优先结合抗原 - 独特型独特复合物的单一结合位点。此外,该因子带有I - J决定簇,这与我们之前在类似TH2细胞表面检测到的情况一致。总体而言,这些结果表明,鉴于T细胞杂交瘤LOP 1.4能够通过产生一种对抗原和独特型都具有亲和力的可溶性因子来增强针对特定抗原的独特型反应,它是一种类似TH2的细胞(支持多种TH亚群的概念)。此外,与I - J + TH2细胞一样,LOP 1.4因子也带有I - J区域决定簇。(摘要截选至400字)

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