MOLECULAR MECHANISM FOR THE FORMATION OF THE HIGH-AFFINITY COMPLEX OF INTERLEUKIN-2 AND ITS RECEPTOR

  • 1 April 1988
    • journal article
    • research article
    • Vol. 5  (2) , 123-138
Abstract
Interleukin 2 (IL-2) binds to its receptors with three distinct affinities, with Kd values of 10-11 M (high), 10-9 M (intermediate) and 10-8M (low). IL-2 responding cells express two proteins that bind IL-2, i.e.a 55 .times. 103 Mr protein (p55 or L chain), which has classically been known as the IL-2 receptor and a second 75 .times. 103 Mr chain (p75 or H chain) with intermediate affinity. Experiments were performed to clarify the mechanism of the high-affinity site formation. Crosslinking of human IL-2 with a high-affinity sites of human T lymphocytes yielded a 150 .times. 103 Mr ternary complex consisting of IL-2, L and H chains. The ternary complex with human IL-2 was formed on EL/Tac 3 cells expressing human L and murine H chains, although human IL-2 was unable to bind to the parental EL-4cell, which does not express human L chain. The high-affinity ternary complex was stable during solubilization and fractionated by gel-filtration chromatography, and the numbers of these complexes were quantified by this method. The number of high-affinity sites on the CT/hR-1 cells, which express the human L, murine L and murine H chains, was almost constant even when either the human or murine L chain was blocked by specific antibodies in agreement with a previous observation. These results indicate that the L and H chains do not form a stable binary complex by themselves and that IL-2 binding induces the formation of the stable high-affinity ternary complex.