THE ALPHA-CHAIN OF THE IL-2 RECEPTOR DETERMINES THE SPECIES-SPECIFICITY OF HIGH-AFFINITY IL-2 BINDING

Interleukin 2 (IL-2) mediated signalling results from ligand binding a nd subsequent heterodimerization of IL-2r beta and gamma(c). The high- affinity IL-2 receptor (IL-2r) is a heterotrimer comprised of the IL-2 r alpha, IL-2r beta and gamma(c) subunits. Whereas human IL-2 effectiv ely binds to either human or murine lymphocytes, murine IL-2 binds wit h markedly higher affinity to murine receptor complexes than to human complexes, Using cell lines stably expressing heterotrimeric IL-2r tha t vary in the species origin of individual subunits, we have demonstra ted that IL-2r alpha is primarily responsible for the species specific ity of IL-2 binding, Studies of ligand binding to the low affinity rec eptor demonstrated that IL-2r alpha displays a similar species prefere nce to the heterotrimeric complex, Moreover, differences in ligand bin ding are reflected in differences in proliferation, A cell line expres sing human IL-2r alpha and IL-2r beta along with murine gamma(c) vigor ously proliferated only in response to human IL-2 at low doses, while both human and murine IL-2 stimulated proliferation of a cell line con taining murine IL-2r alpha (as well as human IL-2r beta and murine gam ma(c)). Therefore, IL-2r alpha is the chain primarily responsible for the species specificity of ligand binding. (C) 1996 Academic Press Lim ited