Structure—Function Relations for the Interleukin-2 Receptor
The original study of IL-2 binding to activated lymphocytes (Robb et al., 1981) described a high-affinity receptor—ligand interaction that fit nicely with the extremely low concentrations of IL-2 that were necessary to promote cellular proliferation. Subsequent investigations, however, indicated that the interaction of IL-2 with cells was not so simple. In particular, antibodies to the IL-2 receptor detected far more receptor molecules on the cell surface than high-affinity IL-2 binding sites (Leonard et al.,1982). As IL-2 became more plentiful, the IL-2 binding assays were extended to higher concentrations of ligand, revealing a second class of low-affinity sites (Robb et al.,1984). The latter sites appeared to account for most or all of the discrepancy between the number of receptors detected with antibodies and the original numerical estimates of high-affinity binding sites. The molecular basis for the two affinity classes of receptor, however, remained unclear. Possible explanations included: (1) the high-and low-affinity sites consisted of distinct IL-2 binding molecules; (2) the affinity difference occurred as a result of variable post-translational modifications of a single IL-2-binding molecule; (3) the difference arose from conformational changes in a single receptor protein, perhaps as a result of homodimer formation or association with a second receptor subunit; and (4) the difference was caused by the effect of a second receptor subunit, present in high-affinity binding sites, which partici-pated directly in ligand binding. In the past year, several laboratories have obtained evidence that the last explanation is indeed the basis for the multiple affinities of the IL-2 receptor.
KeywordsLysine Trypsin Disulfide Inositol Kato
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