Characterization of IgG FcR-mediated proliferation of human T cells induced by mouse and human anti-CD3 monoclonal antibodies. Identification of a functional polymorphism to human IgG2 anti-CD3.

摘要: T cell activation induced by mouse anti-CD3 mAb has shown to be dependent on the Ig isotype of these antibodies. A study dependency human antibodies, however, seems more relevant effector systems, especially in view availability humanized antibodies for clinical applications. We constructed a panel and mouse/human chimeric mAb, which differ only their CH region hence have identical binding sites affinity. By using we now studied ability induce proliferation PBMC analyzed classes IgG FcR involved responses. The (h)IgG1, hIgG3, hIgG4, as well (m)IgG2a mIgG3 an Fc gamma RI (CD64)-dependent all donors. Activation with hIgG2 mIgG1 was observed mediated via low affinity RII (CD32). It found that leukocytes normal donor population display functional polymorphism respect responsiveness. This inversely related previously defined RII-polymorphism mAb. Monocytes expressing responder (LR) allele support efficiently, whereas cells homozygous high (HR) do not. observation could confirmed studies hFc RIIa-transfected fibroblasts, either HR or LR RII-encoding cDNA.