Torimoto Y, Sugita K, Weinberg D S, Dang N H, Donahue C, Letvin N L, Schlossman S F, Morimoto C
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1991 Apr 1;146(7):2176-84.
We have developed a mAb anti-6C2, by immunizing mice with T cell line derived from the Callithrix jacchus (common marmoset). Anti-6C2 is reactive with approximately 50% of unfractionated T cells, 50% of CD4+ cells, and 40% of CD8+ cells. Regarding CD4+ cells, anti-6C2-reactive cells substantially overlap with the CD29+CD45RO+ Th cell population. Moreover, anti-6C2 can divide these T cells into 6C2+ and 6C2- subpopulations. The CD4+CD45RO+6C2+ cells maximally respond to soluble Ag such as tetanus toxoid and provide strong helper function for PWM-driven B cell IgG synthesis. Most interestingly, anti-6C2 was also reactive against activated B cells but not resting B cells; furthermore, this epitope was inducible through activation of resting B cells or B cell line. Biochemical characterization showed that anti-6C2 precipitated two glycoproteins with the relative molecular weights of 180,000 and 95,000 from 125I-surface labeled cell lysate. Sequential immunoprecipitation studies demonstrated that these two glycoproteins were the lymphocyte function-associated antigen (LFA-1) Ag complex (CD11a/18). Significantly, although this antibody did not inhibit cytotoxic killer T cell responses and Ag-induced T cell proliferation as did conventional anti-LFA-1, it did inhibit PWM-driven B cell IgG synthesis. Because 6C2 expression was induced after B cell activation, the above results strongly suggest that the 6C2 molecule may play a role in the interaction of CD4 helper cells and activated B lymphocytes.
我们通过用来自普通狨猴(Callithrix jacchus)的T细胞系免疫小鼠,开发出了一种抗6C2单克隆抗体。抗6C2与约50%的未分级T细胞、50%的CD4⁺细胞和40%的CD8⁺细胞发生反应。对于CD4⁺细胞,抗6C2反应性细胞与CD29⁺CD45RO⁺辅助性T细胞群体有大量重叠。此外,抗6C2可将这些T细胞分为6C2⁺和6C2⁻亚群。CD4⁺CD45RO⁺6C2⁺细胞对破伤风类毒素等可溶性抗原反应最强,并为PWM驱动的B细胞IgG合成提供强大的辅助功能。最有趣的是,抗6C2也与活化的B细胞反应,但不与静止的B细胞反应;此外,该表位可通过静止B细胞或B细胞系的活化诱导产生。生化特性表明,抗6C2从¹²⁵I表面标记的细胞裂解物中沉淀出两种相对分子质量分别为180,000和95,000的糖蛋白。连续免疫沉淀研究表明,这两种糖蛋白是淋巴细胞功能相关抗原(LFA-1)抗原复合物(CD11a/18)。值得注意的是,尽管该抗体不像传统抗LFA-1那样抑制细胞毒性杀伤性T细胞反应和抗原诱导的T细胞增殖,但它确实抑制PWM驱动的B细胞IgG合成。由于B细胞活化后诱导了6C2表达,上述结果强烈表明6C2分子可能在CD4辅助性T细胞与活化的B淋巴细胞相互作用中发挥作用。