SELF-ASSOCIATION OF INTERLEUKIN-2 BOUND TO ITS RECEPTOR

Although radioiodinated interleukin 2 (IL-2) has been used to define t he binding characteristics of the cytokine to the alpha chain of the r eceptor complex, we have found that unsubstituted IL-2 behaves differe ntly. Whereas previous investigations with radioiodinated IL-2 have sh own binding to the alpha chain with a K-d of 10 nM, we show that unsub stituted IL-2 binds to the alpha chain but does not reach saturation b etween 100 and 1000 nM. The explanation for the discrepancy between th e analysis of radioiodinated and unsubstituted cytokine involves the p ropensity of unsubstituted IL-2 for self-association, a property that is abrogated by radioiodination. The functional relevance of our findi ngs is indicated by the different capacities of unsubstituted and iodi nated cytokine to induce prolonged proliferation of human T lymphocyte s.