Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex.
Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex.
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T44分子参与T细胞活化的抗原独立途径。分析与T细胞抗原受体复合物复合物的相关性。
DOI：
10.1084/jem.162.3.823
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发表时间：
1985-09-01
影响因子：
15.3
通讯作者：
Moretta, L
中科院分区：
文献类型：
--
作者：
Moretta, A;Pantaleo, G;Lopez-Botet, M;Moretta, L
先前的研究表明，定义 44 kD T 谱系特异性糖蛋白 (T44) 的 9.3 单克隆抗体 (mAb) 可增强外周血 T 淋巴细胞对植物血凝素 (PHA) 或同种异体细胞的增殖反应。通过间接免疫荧光和流式细胞荧光测定法评估，T44 分子在静息和激活的 T 淋巴细胞以及胸腺细胞亚群中表达。鉴于 T44 在 T 细胞激活中的潜在重要性，我们研究了 9.3（抗 T44）抗体在培养条件下刺激外周血 T 淋巴细胞的能力，从而对抗 T3 mAb 产生最佳增殖反应。与 UCHT1（抗 T3）mAb 一样，9.3（抗 T44 mAb）可促进纯化 T 细胞的强烈增殖反应，前提是将贴壁细胞添加到培养物中。在第 5 天（使用抗 T3 或 PHA 在第 3 天）始终检测到对 9.3 抗体的最大增殖反应。此外，用 9.3 抗体触发 T 淋巴细胞（在贴壁细胞存在的情况下）导致大量 IL-2 产生，并在 48 小时达到峰值。在诱变的 jurkat T 白血病细胞系上对 T44 分子和参与 T 细胞激活的其他分子（包括克隆型限制的 Ti 和单态 T3 或 T11 分子）之间的物理和功能关系进行了分析。这种突变体称为 JA3（表面表型：T11+、T3+、3A1+、T4-、T8-、DR-、Tac-、4F2+、T44+），经 PHA、抗 T3 或抗克隆型单克隆抗体与佛波醇肉豆蔻酸酯乙酸酯（或贴壁细胞）刺激后，产生大量 IL-2。在还原条件下，来自 125I 标记的 JA3 细胞的抗 T44 mAb 沉淀的分子表现为 Mr 40-45,000 的弥散条带；在非还原条件下，观察到 Mr 80-85,000 的显着带，而 Mr 40-45,000 带则大大减少。因此，T44分子在还原和非还原条件下都具有与携带克隆型(Ti)决定簇的分子相似的相对分子量。此外，与抗 Ti 或抗 T3 mAb 一样，抗 T44 抗体在佛波醇肉豆蔻酸酯乙酸酯存在下诱导 JA3 细胞产生大量 IL-2。 T44 和携带克隆型结构的分子之间的其他相似之处包括对抗体诱导的调节的敏感性以及调节后在细胞表面的晚期重新表达（72 小时）。总而言之，这些实验表明抗 T44 mAb 可能识别 T 细胞受体分子的单态决定簇，或者在物理或功能上与 T3-Ti 复合物连接。（摘要截断为 400 字）
Prior studies indicate that the 9.3 monoclonal antibody (mAb) which defines a 44 kD T lineage-specific glycoprotein (T44) enhances the proliferative response of peripheral blood T lymphocytes to phytohemagglutinin (PHA) or allogeneic cells. The T44 molecule was expressed in both resting and activated T lymphocytes and in a subset of thymocytes, as assessed by indirect immunofluorescence and flow cytofluorometry. In view of the potential importance of T44 in T cell activation, we investigated the ability of the 9.3 (anti-T44) antibody to stimulate peripheral blood T lymphocytes under culture conditions giving optimal proliferative responses to anti-T3 mAb. Like UCHT1 (anti- T3) mAb, the 9.3 (anti-T44 mAb) promoted strong proliferative responses of purified T cells, provided that adherent cells were added to the culture. Maximal proliferation in response to 9.3 antibody was consistently detected at day 5 (at day 3 with anti-T3 or PHA). Moreover, triggering of T lymphocytes with 9.3 antibody (in the presence of adherent cells) resulted in strong IL-2 production that peaked at 48 h. Analysis of the physical and functional relationship between the T44 molecule and other molecules involved in T cell activation, including the clonotypically restricted Ti and the monomorphic T3 or T11 molecules, was carried out on a mutagenized jurkat T leukemia cell line. This mutant, termed JA3 (surface phenotype: T11+, T3+, 3A1+, T4-, T8-, DR-, Tac-, 4F2+, T44+) produced large amounts of IL-2 upon stimulation with PHA, anti-T3, or anticlonotypic mAb in conjunction with phorbol myristate acetate (or adherent cells). The molecules precipitated by anti-T44 mAb from 125I- labeled JA3 cells appeared as a diffuse band of Mr 40-45,000 under reducing conditions; under nonreducing conditions, a prominent band of Mr 80-85,000 was observed, while the Mr 40-45,000 band was greatly reduced. Thus, T44 molecules in both reducing and nonreducing conditions had relative molecular weights similar to that of molecules carrying clonotypic (Ti) determinants. In addition, like anti-Ti or anti-T3 mAb, anti-T44 antibody induced JA3 cells to produce large amounts of IL-2 in the presence of phorbol myristate acetate. Other similarities between T44 and molecules carrying clonotypic structures included the susceptibility to antibody-induced modulation and the late reexpression (72 h) at the cell surface after modulation. Taken together, these experiments suggest that anti-T44 mAb might recognize a monomorphic determinant of the T cell receptor molecule or be physically or functionally linked to the T3-Ti complex.(ABSTRACT TRUNCATED AT 400 WORDS)