Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies.
The human high-affinity receptor for interleukin 2 (IL-2) has been proposed as being a membrane complex composed of at least two distinct polypeptide chains: p55 (alpha chain), recognized by the anti-Tac monoclonal antibody (mAb), and p75 (beta chain), both of which are capable of binding IL-2. Whereas the alpha chain itself has been shown to be nonfunctional, the beta chain appears to be pivotal in the IL-2 signal transduction, although the beta chain is otherwise poorly characterized. Three beta chain-specific mAbs, designated Mik-beta 1, -beta 2, and -beta 3, were developed. Mik-beta 1 and -beta 2 completely inhibited the IL-2 binding to the beta chain, whereas Mik-beta 3 immunoprecipitated the beta chain crosslinked with 125I-labeled IL-2. The beta chain immunoprecipitated by these mAbs was revealed to have a Mr of 68,000-72,000. High-affinity IL-2 binding was completely abolished by Mik-beta 1. Although IL-2-dependent T-cell growth at high IL-2 concentrations was not inhibited by the anti-Tac, it was almost completely inhibited by Mik-beta 1 in the presence of the anti-Tac. These results clearly indicate that the beta chain is an indispensable component to the high-affinity IL-2 receptor and is responsible for the IL-2 signal transduction. The beta chain was found to be constitutively expressed without the alpha chain on the surface of peripheral blood Leu-19+ natural killer cells.
Tsudo
M
M
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Kitamura
F
F
Miyasaka
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007163:Immunosorbent Techniques; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D007694:Killer Cells, Natural; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000276:immunology; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2