Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies.

Abstract

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 of 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.