Lefrançois L, Bevan M J
J Immunol. 1985 Jul;135(1):374-83.
This report describes the production and characterization of MAb specific for neoantigenic determinants, called CT antigens, present on the T200 glycoprotein of CTL. The CT determinants are expressed at high levels only on activated CTL. Although differences had previously been noted in the cell surface protein profile of distinct T cell subsets, this is the first description of a lineage-specific activation antigen. Furthermore, these determinants appear to have functional significance, because the CT-specific MAb block cytolytic function. Immune precipitation experiments indicated that the appearance of the CT antigens correlated with m.w. changes and the appearance of additional T200 protein species that were CTL specific. MLC cells cultured in the presence of IL 2-containing supernatants undergo a gradual shift from relatively low CT antigen expression to very high CT expression. This shift is accompanied by modifications of T200 eventually leading to a T200 protein profile identical to that of CTL clones. However, MLC cells propagated without the addition of IL 2-containing supernatants do not undergo a shift in CT antigen expression. Thus, the extent to which modifications occur in the T200 molecule is regulated by soluble factors. Competitive binding assays with two CT-specific MAb indicated that at least two distinct but overlapping neo-epitopes appear as the result of the T200 alterations. In sum, we have discovered the presence of CTL-lineage-specific activation antigens whose expression is regulated by lymphokines and is linked to cytolytic function. MAb specific for determinants such as these could be invaluable tools in the enumeration and depletion of specific T cell subsets in in vivo situations.
本报告描述了针对新抗原决定簇(称为CT抗原)的单克隆抗体(MAb)的产生和特性,这些抗原存在于CTL的T200糖蛋白上。CT决定簇仅在活化的CTL上高水平表达。尽管先前已注意到不同T细胞亚群的细胞表面蛋白谱存在差异,但这是对谱系特异性活化抗原的首次描述。此外,这些决定簇似乎具有功能意义,因为CT特异性MAb可阻断细胞溶解功能。免疫沉淀实验表明,CT抗原的出现与分子量变化以及CTL特异性的额外T200蛋白种类的出现相关。在含IL-2上清液存在下培养的MLC细胞经历从相对低水平的CT抗原表达逐渐转变为非常高水平的CT表达。这种转变伴随着T200的修饰,最终导致T200蛋白谱与CTL克隆相同。然而,在不添加含IL-2上清液的情况下繁殖的MLC细胞不会发生CT抗原表达的转变。因此,T200分子中修饰发生的程度受可溶性因子调节。用两种CT特异性MAb进行的竞争性结合试验表明,至少两个不同但重叠的新表位是T200改变的结果。总之,我们发现了CTL谱系特异性活化抗原的存在,其表达受淋巴因子调节并与细胞溶解功能相关。针对此类决定簇的MAb可能是体内情况下计数和清除特定T细胞亚群的宝贵工具。