Monoclonal antibodies identify three epitope clusters on the mouse p55 subunit of the interleukin 2 receptor: relationship to the interleukin 2-binding site.

A new rat monoclonal antibody (5A2) directed against the mouse interleukin 2 receptor (IL2R) is described. This antibody binds specifically to IL2R+ cells, competes with both cold IL2 and 125I-labeled IL2 for the IL2-binding site and inhibits IL2-induced T cell proliferation. This reagent was compared to five previously characterized rat monoclonal antibodies directed against the p55 subunit of the mouse IL2R. The capacity of all the antibodies to inhibit IL2-induced T cell proliferation was assessed. The relationship of these eight antibodies to each other and to the IL2-binding site was studied by cross-inhibition assays, and by Scatchard analysis of the data. The results indicate that the six monoclonal antibodies recognize epitopes in three areas of the p55 subunit of the mouse IL2R. Antibodies against two of the clusters affect IL2 binding. One cluster defined by 3 antibodies is probably located in the area of the IL2-binding site as there is competitive inhibition between IL2 and antibodies against this cluster. A single antibody directed against an epitope outside this cluster appears to inhibit IL2 binding by inducing a conformational change in the p55 subunit of the IL 2R. Two other antibodies identify a third region which is not involved in the formation of the binding site.