SUBSTITUTIONS AT THE GLU(62) RESIDUE OF HUMAN INTERLEUKIN-2 DIFFERENTIALLY AFFECT ITS BINDING TO THE ALPHA-CHAIN AND THE BETA-GAMMA COMPLEXOF THE INTERLEUKIN-2 RECEPTOR

Human interleukin-2 (IL-2) alpha helix B is more conserved than the wh ole molecule, but has been less studied than other a helices of IL-2. Using site-directed mutagenesis, several IL,-2 mutants in this helix w ere obtained. We found that the IL-2 mutant containing Leu at position 62 (Leu(62)-IL-2) loses its ability to bind IL-2 receptor subunit alp ha (IL-2R alpha), but retains binding affinity to IL-2R subunit beta g amma as well as some bioactivity; nevertheless, another substitution a t the same residue, Arg(62) IL-2, loses its binding ability to both IL -2R alpha and IL-2R beta gamma, and can no longer stimulate IL-2-depen dent cell growth, showing that Glu(62) not only takes part in IL-2R al pha binding, but can also affect IL-2 binding to IL-2R beta gamma. In this regard, Glu(62) may be a key site in the IL-2/IL-2R alpha interac tion, and can facilitate IL-2R ternary-complex formation, leading to I L-2R alpha-mediated, IL-2-stimulated signal transduction.