Background
The OKT3 antibody binds to CD3 epsilon of the T cell receptor-CD3 complex found only on mature T cells and medullary thymocytes. An interaction between T cells, OKT3, and monocytes causes T-cell activation (mitogenesis) in vitro. On the other hand, the OKT3 antibody blocks the unique association between the antigen receptor and CD3, and both the generation and function of cytotoxic T cells. After an initial dose of the OKT3 antibody, T cells disappear from the circulation within minutes to hours. During treatment with the OKT3 antibody, T cells bearing the usual array of surface molecules (CD2, CD4, and CD8) reappear in the peripheral blood circulation but these cells are devoid of CD3. After another 48 hours without the OKT3 antibody, the normal array of surface molecules including CD3 appear again on all T cells. The selective removal of CD3 by internalization is thought to be the key mechanism of action of the OKT3 antibody. Comodulation of the antigen receptor with CD3 explains the immunoblocking action of the OKT3 antibody in vivo. The OKT3 antibody is ineffective clinically if the CD3 target molecule is not modulated.