Berg J, Lötscher E, Steimer K S, Capon D J, Baenziger J, Jäck H M, Wabl M
Department of Microbiology and Immunology, University of California, San Francisco 94143-0414.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4723-7. doi: 10.1073/pnas.88.11.4723.
Although AIDS patients lose human immunodeficiency virus (HIV)-specific cytotoxic T cells, their remaining CD8-positive T lymphocytes maintain cytotoxic function. To exploit this fact we have constructed bispecific antibodies that direct cytotoxic T lymphocytes of any specificity to cells that express gp120 of HIV. These bispecific antibodies comprise one heavy/light chain pair from an antibody to CD3, linked to a heavy chain whose variable region has been replaced with sequences from CD4 plus a second light chain. CD3 is part of the antigen receptor on T cells and is responsible for signal transduction. In the presence of these bispecific antibodies, T cells of irrelevant specificity effectively lyse HIV-infected cells in vitro.
尽管艾滋病患者会失去人类免疫缺陷病毒（HIV）特异性细胞毒性T细胞，但他们剩余的CD8阳性T淋巴细胞仍保持细胞毒性功能。为利用这一事实，我们构建了双特异性抗体，可将任何特异性的细胞毒性T淋巴细胞导向表达HIV gp120的细胞。这些双特异性抗体包含来自抗CD3抗体的一个重链/轻链对，与一个重链相连，该重链的可变区已被来自CD4的序列以及第二条轻链取代。CD3是T细胞抗原受体的一部分，负责信号转导。在这些双特异性抗体存在的情况下，无关特异性的T细胞可在体外有效裂解HIV感染的细胞。
