Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen.

Abstract

Interleukin 2 promotes proliferation of T cells by virtue of its interaction with a high-affinity cell surface receptor. This receptor is a 55,000 mol wt glycoprotein that is also recognized by the murine monoclonal antibody, anti-Tac. Quantitative binding studies with radiolabeled IL-2 and anti-Tac, however, initially indicated far more antibody binding sites per cell than IL-2 binding sites. Extension of the IL-2 binding analysis to concentrations several thousand-fold higher than that necessary for the T cell proliferative response demonstrated the existence of a class (or classes) of low-affinity IL-2 binding sites. Inclusion of the low-affinity IL-2 binding greatly reduced the quantitative discrepancy in the ligand binding assays. That the low-affinity binding, as well as the high-affinity interaction, was associated with the Tac molecule was indicated by the finding that the antibody could substantially or totally block the entire spectrum of IL-2 binding and by the finding that IL-2 could in turn block all radiolabeled anti-Tac binding. The low-affinity sites were found on activated T cells, several human and murine T cell lines and two examples of Tac-positive B cells. The physiological role of the low-affinity IL-2 binding sites and the molecular changes in the Tac protein that give rise to the affinity differences remain open to investigation.

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

“…The IL-2 receptor family comprises three single-pass transmembrane proteins, IL-2Ra (p55, CD25), IL-2Rb (p75, CD122), and IL-2Rg (p64, CD132) (Robb et al 1981(Robb et al , 1984bLeonard et al 1984Leonard et al , 1985Greene et al 1986;Hatakeyama et al 1989;Tsudo et al 1990;Takeshita et al 1992;Noguchi et al 1993). IL-2Ra is present at low concentrations on T cells and is expressed along with IL-2 following TCR activation, forming a transient autocrine/paracrine signaling loop.…”

Decreased production of soluble interleukin 2 receptor by phytohaemagglutinin-stimulated peripheral blood mononuclear cells in patients with breast cancer after adjuvant therapy

“…Interleukin 2 leads to the proliferation of T cells via its receptor which is expressed on activated, but not resting T cells (Greene et al, 1986;Wang & Smith, 1987) and which can be induced by mitogenic stimulation (Robb et al, 1984). The membrane-bound interleukin 2 receptor can be released and transformed into a soluble form (Levy et al, 1987) which -although not completely identical (Rubin et al, 1986;Yannic et al, 1987) -retains its ability to bind interleukin 2 (Rubin et al, 1986).…”

Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R.

“…These cells are activated by soluble I1.-2 after its interaction with specific cell surface receptors. The I1.2R is made up of at least two subunits, o~ (p55, Tac) and ~ (p70-75), that noncovalently associate on the cell surface to produce a high-affnity receptor complex capable of binding II.-2 with an equilibrium Ka of ~5-20 pM (4)(5)(6)(7)(8)(9). Each of the chains present in the I1.2R complex can bind I1.2 independently of the other, with either low (o~, Kd = 5-20 nM) or intermediate (fl, Ka = 0.5-2.0 nM) affinity (2,(7)(8)(9)(10)(11).…”