Qi Y, Staerz U D
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Nat Biotechnol. 1998 Mar;16(3):271-5. doi: 10.1038/nbt0398-271.
T lymphocytes are crucial in the defense against foreign intruders and cancerous growths. Yet, in circumstances such as transplantation or autoimmunity, T-cell-mediated responses can be detrimental. Inhibition of these deleterious responses is currently achieved by drugs that induce general immune suppression. These compounds also impair the patient's defenses against infections. Strategies are now being sought that induce selective rather than generalized immune unresponsiveness. One such strategy is the ability to inhibit the activation of CD8+ T lymphocytes. As CD4+ T lymphocytes similarly participate in graft rejection and in autoimmune diseases, we have now developed a reagent to delete their activity. It comprises CD4 and an anti-MHC class II antibody. By virtue of the antibody's specificity for MHC class II molecules, this hybrid antibody (Hab) binds to class II molecules, thereby bringing CD4 accessory molecules to the surface of class II-bearing stimulator cells where they occupy CD4 binding sites on class II molecules. As a consequence CD4+ T cells with specificity to Hab-coated stimulator cells cannot engage their CD4 molecules and are no longer activated. This Hab technology provides a strategy to offer specific rather than generalized immune suppression.
T淋巴细胞在抵御外来入侵者和癌症生长方面至关重要。然而，在移植或自身免疫等情况下，T细胞介导的反应可能是有害的。目前，通过诱导全身免疫抑制的药物来抑制这些有害反应。这些化合物也会削弱患者对感染的防御能力。现在正在寻找能够诱导选择性而非全身性免疫无反应的策略。一种这样的策略是抑制CD8+T淋巴细胞的激活能力。由于CD4+T淋巴细胞同样参与移植物排斥和自身免疫性疾病，我们现在已经开发出一种试剂来消除它们的活性。它由CD4和抗MHC II类抗体组成。凭借该抗体对MHC II类分子的特异性，这种杂交抗体（Hab）与II类分子结合，从而将CD4辅助分子带到携带II类分子的刺激细胞表面，在那里它们占据II类分子上的CD4结合位点。结果，对Hab包被的刺激细胞具有特异性的CD4+T细胞无法结合其CD4分子，不再被激活。这种Hab技术提供了一种提供特异性而非全身性免疫抑制的策略。
