Activation properties of T cell receptor-gamma delta hybridomas expressing diversity in both gamma- and delta-chains.
Activation properties of T cell receptor-gamma delta hybridomas expressing diversity in both gamma- and delta-chains.
复制标题
T 细胞受体-γ δ 杂交瘤的激活特性，表达γ 链和δ 链的多样性。
作者：
S. MARUSIC;D. Pardoll;T. Saito;O. Leo;B. Fowlkes;J. Coligan;R. Germain;R. Schwartz;A. Kruisbeek
为了阐明小鼠T_3受体的结构、多样性和激活特性，对表达T细胞受体(T细胞受体)的4个克隆的T细胞杂交瘤进行了T细胞受体(T细胞受体)基因转录、激活特性和淋巴因子产生的检测。对这些杂交瘤上表达的伽马和Delta蛋白进行的生化分析显示，在这些杂交瘤的来源Dly-1 Lyt-2-L3T4-胸腺细胞的整个群体中没有观察到新的伽马和Delta物种。因此，在克隆水平上对TCR-Gamma Delta复合体的表达分析表明，在纯合子近交系小鼠中，Gamma和Delta似乎都作为多个不同的基因产物表达。Northern印迹分析表明，所有的Gamma Delta杂交瘤都有成熟的1.5kb的TCR-α链和成熟的TCR-伽马链转录本，但没有一个杂交瘤有成熟的1.3kb的TCR-β链转录本，这表明TCR异源二聚体的类型反映了这些杂交瘤TCR基因转录的状态。我们的结果还揭示了TCR-Gamma Delta和TCR-Alphaβ细胞在激活特性方面的惊人相似之处。首先，与伽马三角洲复合体相关的所有五个T3组分的大小和糖基化模式与与α-β-异二聚体相关的那些组分相同。其次，在这些伽马三角洲细胞中，功能的诱导(通过淋巴因子的产生)也可以通过各种已知的刺激来实现，这些刺激也可以在α-β细胞中诱导激活信号：直接的受体参与(即通过抗Thy-1)和佛波醇12-肉豆蔻酸盐13-醋酸酯加离子霉素介导的。总而言之，这些发现表明，伽马三角洲T细胞表达一种至少有限多样性的受体，并使用与携带TCR-αβ的T细胞非常相似的T3介导的激活途径。
To elucidate the structure, diversity, and activation properties of the murine T3-associated gamma delta-receptor, examination was made of the gamma delta and T3 components, T cell receptor (TCR) gene transcription, activation properties, and lymphokine production in a panel of four cloned T cell hybridomas expressing a TCR-gamma delta. Biochemical analysis of the gamma and delta proteins expressed on these hybridomas reveals new gamma and delta species not observed in whole populations of dLy-1 Lyt-2-L3T4-thymocytes from which these hybridomas were derived. Thus, analysis of expression of the TCR-gamma delta complex at the clonal level indicates that both gamma and delta appear to be expressed as multiple distinct gene products within a homozygous inbred mouse strain. Northern blot analysis reveals that, whereas all gamma delta hybridomas had mature 1.5-kb TCR-alpha-chain and mature TCR-gamma-chain transcripts, none had mature 1.3-kb TCR-beta-chain transcripts, thus indicating that the type of TCR heterodimer expressed reflects of the state of TCR gene transcription in these hybridomas. Our results also reveal striking similarities between TCR-gamma delta and TCR-alpha beta cells with respect to their activation properties. First, all five of the T3 components associated with the gamma delta-complex are of the same size and have the same glycosylation patterns as those associated with alpha beta-heterodimers. Second, induction of function in these gamma delta cells (assayed by lymphokine production) can be achieved with a variety of stimuli known to elicit activation signals in alpha beta cells as well: direct receptor-engagement (i.e., through anti-Thy-1), and phorbol 12-myristate 13-acetate-plus-ionomycin-mediated. Collectively, these findings suggest that gamma delta T cells express a receptor of at least limited diversity and use T3-mediated activation pathways very similar to those employed by TCR-alpha beta-bearing T cells.