Interleukin 2 high-affinity receptor expression requires two distinct binding proteins.
A cell line established from a patient with acute lymphoblastic leukemia was found to express IL-2 binding sites with a novel, intermediate affinity compared with the characteristic high-affinity IL-2-receptors and low-affinity IL-2 binding sites described previously. Clones were isolated from this cell line that displayed solely this new IL-2-binding protein, and were found to be unreactive with anti-Tac, the mAb that competes with IL-2 for binding. Moreover, these same cloned cells did not express mRNA detectable by hybridization with radiolabeled cDNA encoding the Tac protein. In contrast, the original cell line and similar clones expressed low levels of Tac mRNA and cell surface Tac antigen, both of which could be augmented by exposure to medium conditioned by adult T leukemia cell lines. Particularly noteworthy, induction of Tac antigen expression was paralleled by an increase in the number of high-affinity IL-2-R detectable. Since the expression of the Tac antigen protein by itself makes only for low-affinity IL-2 binding, these data prompted a reevaluation of the structural composition of high-affinity IL-2-R. Analysis of the IL-2-binding proteins expressed by leukemic cell lines lacking high-affinity receptors revealed only a single protein, larger than the Tac antigen protein (Mr = 75,000 vs. 55,000). In contrast, clones induced to express high-affinity receptors had clearly both of these IL-2-binding proteins. Moreover, when IL-2 binding to normal T cells was performed under conditions that favored the proportion of high-affinity receptors occupied, two distinct proteins identical to those already identified on the leukemic cells could be crosslinked covalently to radiolabeled IL-2. The interpretations derived from these varied, assembled data, point to two IL-2-binding proteins, both of which are required for high-affinity IL-2 binding.
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D046911:Macromolecular Substances; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2