Uggla C K, Geisberg M, Jondal M, Knowles R W
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Scand J Immunol. 1989 May;29(5):507-15. doi: 10.1111/j.1365-3083.1989.tb01153.x.
Two monoclonal antibodies (MoAb), 9-1 (anti-CD2) and 3G8 (anti-CD16), were previously shown to enhance the cytotoxic activity of human natural killer (NK) cells. The present study examined the effect of 9-1 and 3G8 with different effector and target cells to determine whether they activate NK cells through a common mechanism. Analysis of purified lymphocyte subpopulations demonstrated that the CD3+CD16+CD3- NK effector cell population is enhanced by both antibodies, while purified CD2+CD16-CD3+ T cells are not activated by either antibody. Although both antibodies enhance killing of K-562 and Daudi, killing of T-cell lines is enhanced by 9-1 and inhibited by 3G8. In contrast, killing of the promyelocytic cell line, U-937 is inhibited by 9-1 and enhanced by 3G8. On NK-susceptible cells the pattern of enhancement with 3G8, an IgG1 MoAb, is consistent with the pattern of target cell expression of an Fc receptor, FcR II, known to bind IgG1 antibodies. This suggests that 3G8 may cross-link effector and target cells through CD16 on the effectors and FcR II on these targets. This could activate NK killing by a mechanism similar to antibody-dependent cellular cytotoxicity reactions (ADCC) with the MoAb in the reverse orientation. The failure of 3G8 F(ab')2 fragments to enhance NK killing, further supports the reverse ADCC mechanism of enhancement by 3G8. The pattern of enhancement mediated by 9-1, an IgG3 MoAb, is not correlated with any target cell Fc-receptor known to bind IgG3 MoAb. The effect of 9-1 may result, instead, from its binding to the unique 9-1 epitope on the CD2 molecule involved in CD2-mediated T-cell activation, as previously described. Alternative mechanisms, including activation of NK killing by 9-1 mediated cross-linking of CD2 and CD16 on the effector cells, have also been discussed.
两种单克隆抗体（MoAb），9-1（抗CD2）和3G8（抗CD16），先前已被证明可增强人类自然杀伤（NK）细胞的细胞毒性活性。本研究检测了9-1和3G8与不同效应细胞和靶细胞的作用，以确定它们是否通过共同机制激活NK细胞。对纯化淋巴细胞亚群的分析表明，两种抗体均可增强CD3 + CD16 + CD3 - NK效应细胞群体，而纯化的CD2 + CD16 - CD3 + T细胞均未被任何一种抗体激活。虽然两种抗体均可增强对K-562和Daudi的杀伤作用，但9-1可增强对T细胞系的杀伤，而3G8则抑制这种杀伤。相反，9-1抑制早幼粒细胞系U-937的杀伤，而3G8则增强这种杀伤。在NK敏感细胞上，IgG1 MoAb 3G8的增强模式与已知可结合IgG1抗体的Fc受体FcR II的靶细胞表达模式一致。这表明3G8可能通过效应细胞上的CD16和这些靶细胞上的FcR II交联效应细胞和靶细胞。这可能通过与MoAb反向的类似于抗体依赖性细胞毒性反应（ADCC）的机制激活NK杀伤。3G8 F(ab')2片段未能增强NK杀伤，进一步支持了3G8增强的反向ADCC机制。IgG3 MoAb 9-1介导的增强模式与已知可结合IgG3 MoAb的任何靶细胞Fc受体均无相关性。相反，9-1的作用可能是由于其与先前所述的参与CD2介导的T细胞活化的CD2分子上独特的9-1表位结合所致。还讨论了其他机制，包括9-1介导的效应细胞上CD2和CD16交联激活NK杀伤。
