Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107.
The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
Osawa
H
H
Institut für Immunologie, Klinikum Steglitz, Freie Universität Berlin, Federal Republic of Germany.
Diamantstein
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D000939:Epitopes; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D000939:Epitopes; D007376:Interleukin-2; D015375:Receptors, Interleukin-2