Molecular Analysis of the Interleukin-2 Receptor Complex: Expression of the Human α and β Chain cDNAs

Abstract

Lymphokines, a class of soluble mediators for intercellular communications are known to play a key role in the regulation of the immune system through interaction with specific receptor(s) on the target cells. Interleukin-2 (IL-2), the first of a series of lymphokines to be discovered and completely characterized, plays a key role in the antigen-specific clonal proliferation of T lymphocytes (T cells). Expression of IL-2 and functional, high-affinity IL-2 receptor (IL-2R) complex is induced in the antigen-activated T cells. IL-2 also acts on other cell types such as B lymphocytes (B cells), macrophages, natural killer cells (NK cells), immature thymocytes and neural cells such as oligodendrocytes (for reviews, see Smith, 1984, 1988; Taniguchi et al., 1986; Merrill, 1987). To date, little has been known about the mechanism(s) of signal transduction in the IL-2 system. The receptor for IL-2 is unique in that the ligand binds to at least two distinct membrane components, giving rise to the expression of high-, intermediate- and low-affinity IL-2R forms with the respective dissociation constants (Kds) of about 10-11M, 10-9M and 10-8M (Robb et al., 1984; Smith, 1988). Following the initial expression studies for the clones human IL-2Rα cDNA, it became evident that IL-2Rα constitutes the low-affinity form and it participates in the formation of the functional, high-affinity IL-2R in association with a specific membrane component(s) of lymphoid cells (Hatakeyama et al., 1985; Kondo et al., 1986; Robb, 1986). Subsequently, such a component was identified to be a novel IL-2 receptor chain, termed IL-2Rβ chain (IL- 2Rβ or p70–75) (Sharon et al., 1986; Tsudo et al., 1986; Teshigawara et al., 1987; Dukovich et al., 1987). Thus the two IL-2R components, the α and β chain, form the heterodimeric high-affinity IL-2R via noncovalent interactions, whereas the β chain alone constitutes the intermediate-affinity IL-2R. Experimental evidence suggests that IL- 2Rβ chain is the main component in driving the IL-2-mediated signal transduction (for review, see Smith, 1988). As an essential step to gain further insight on the molecular basis of the functional (i.e. high-affinity) IL-2R and on the mechanism of IL-2 mediated signal transduction, we have isolated the cDNAs encoding the human IL-2Rβ chain.