Four epitopes on the rat 55‐kDa subunit of the interleukin 2 receptor as defined by newly developed mouse anti‐rat interleukin 2 receptor monoclonal antibodies

Abstract

Four new mouse monoclonal antibodies (mAb), ART-38, ART-35, ART-75 and ART-94, directed against the rat interleukin 2 receptor (IL 2R) have been developed. As shown by immunoprecipitation studies they all recognize specifically the 55-kDa subunit of the rat IL 2R. These mAb were compared to three previously characterized mouse mAb directed against the 55-kDa molecule of the rat IL 2R, namely the ART-18, ART-65 and OX-39 mAb. Out of all seven mAb, only ART-18 and OX-39 were found to inhibit the IL 2 binding to activated T cells, while IL 2R inhibited the binding of ART-18 alone. ART-18 was the only mAb found to inhibit the IL 2-dependent proliferation of cells carrying the IL 2R. Scatchard plot analyses showed gross differences in the numbers of mAb-binding sites ranging between 30,000 (ART-65) and 165,000 (ART-75) as well as in their affinities which ranged between 2.5 X 10(-9) M (ART-38) and 8.3 X 10(-10) M (OX-39). Cross inhibition studies revealed that the mAb recognize four different epitopes on the 55-kDa rat IL 2R subunit.

Effects of depletion of cells bearing the interleukin-2 receptor on immunoglobulin production and allergic airway responses in the rat.

“…ART-I8inhibits IL-2 binding to activated T cells and inhibits the IL-2-dependent proliferation of cells carrying the IL-2 receptor (22). In addition, soluble IL-2 receptors competitively impede ART-I8 binding to lymphocytes, and ART-I8abolishes IL-2 receptor expression on lymphocytes (23).This antibody has been shown to be effective in inhibiting IL-2-dependent T-cell responses in vitro (24) and in inhibiting the in vivo rejection of cardiac (19), renal (25), and pancreatic islet grafts (26).…”

Pathogenesis and mechanisms of graft rejection in concordant xenotransplantation with special reference to hamster‐to‐rat cardiac transplantation

“…The timing of mAb administration in relation to an antigenic challenge may be crucial to achieve an inhibitory effect (162), and the isotypes of mAbs play an important role in terms of ability to mediate antibody dependent cellular cytotoxicity or complement dependent cytolysis (163,164). Furthermore, the binding to different epitopes identified by different mAbs can result in a quite varying in vivo efficacy which besides correlate poorly to in vitvo binding parameters (164,165) and the in vivo effect showed to be not simply dose dependent in our results (62).…”