Unusually restricted anti-isotype human immune response to OKT3 monoclonal antibody.

Abstract

The unusual anti-mouse immunoglobulin (Ig) sensitization of a renal allograft recipient who was treated prophylactically with the anti-T cell monoclonal antibody OKT3 (IgG2a) is reported. Whereas in most patients, the injection of OKT3 (5 mg/day, i.v. for 13 days) induces the rapid appearance of neutralizing anti-OKT3 antibodies, the patient reported here did not show the signs of conventional anti-OKT3 sensitization. High levels of circulating OKT3 persisted and no OKT3+ lymphocytes reappeared during the whole treatment period. Moreover, no IgG or IgM anti-OKT3 antibodies were detected at any time, using a specific enzyme-linked immunosorbent assay. However, an atypical anti-isotype response was evidenced in this subject whose Ig were shown by indirect fluorescence to bind to normal T cells coated with OKT3 or with other anti-T cell murine monoclonal antibodies carrying the IgG2a isotype (no reactivity was observed with IgG1 or IgG2b molecules). The patient's Ig did not bind to normal T cells coated with F(ab')2 fragments of OKT3 and did not inhibit the binding of OKT3 to its target antigen indicating that they reacted with the Fc fragment of the OKT3 molecule. Additionally, and probably explained by this unusual anti-OKT3 response, the patient's Ig were shown to inhibit the phytohemagglutinin-induced proliferation of normal lymphocytes, to bind under selected in vitro conditions to normal T cells and lastly to enhance the antigenic modulation induced in vitro by OKT3 on its membrane receptor.