BriefDefinitive Report CO-INTERNALIZATION OF THE p55 AND p70 SUBUNITS OF THE HIGH-AFFINITY HUMAN INTERLEUKIN 2 RECEPTOR Evidence for a Stable Ternary Receptor Complex BY MARION

Activated human T lymphocytes express both high-affinity (dissociation constant [Kd] -5-70 pM) and low-affinity (Kd 5-30 nM) forms of membrane IL-2-Rs (1, 2) . Cellular proliferative responses as well as receptor-mediated endocytosis of IL-2 appear to be mediated by the high-affinity IL-2-Rs but not by the low-affinity class of receptors (1-3). Recent 1251-IL-2 crosslinking (4-8) and reconstitution studies (6-8) have suggested that the high-affinity receptor corresponds to amembrane complex comprised of at least two different IL-2-binding proteins, p55 (Tac, IL-2-Ra) and p70 (IL-2-RD) . Expression of p55 or p70 alone results in low or intermediate (Kd -0.5-1 nM) IL-2-Rs, respectively (6-8), while coexpression of the p55 and p70 proteins results in high-affinity heterodimeric-binding sites . The p70, but not the p55, protein is capable of internalizing surface-bound IL-2 with kinetics indistinguishable from that of the high-affinity p55/p70 complex (9), suggesting that p70 is the primary component responsible for ligand endocytosis . Although suggestive evidence has been presented for a ternary complex between IL-2 and the noncovalently linked a and R subunit equivalents of the murine IL2-R (10), chemical crosslinking studies have thus far failed to identify a similar trimolecular complex composed of IL-2, p55, and p70 on the surface of human T lymphocytes. Recent studies of the rates of IL-2 association and dissociation have revealed striking differences in ligand binding to the p55, p70, and the heterodimeric high-affinity receptors (11, 12). The interaction of IL-2 with the p55 receptor is characterized by very rapid rates of association and dissociation . In contrast, ligand binding to the p70 protein occurs very slowly. The high-affinity receptor exhibits a composite of these properties with the t1/2 of association resembling p55 and the