CDB15:0000903 IL2 — IL2RA
Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R.
The Journal of experimental medicine, 1992; PubMed, Homo sapiens IL2 — Homo sapiens IL2RA
ABSTRACT: Interleukin 2 (IL-2) receptors expressed on the surface of activated T cells and natural killer (NK) cells exhibit a variety of affinity states depending on their subunit composition. Low-affinity binding is associated with a 55-kDa alpha chain, intermediate-affinity binding with a 70-75-kD beta chain, and high-affinity binding with a bimolecular complex of the alpha and beta subunits. In a previous study of the IL-2 receptors expressed on NK cells obtained from cancer patients after in vivo IL-2 therapy, we documented a discrepancy between the level of beta chain and the level of intermediate-affinity IL-2 binding sites expressed on the cell surface. Based on this result, we postulated that formation of intermediate-affinity receptor sites required a component in addition to the beta chain, and that this component was present at limiting levels in the patient NK cells. In the present study we have examined the structure of the intermediate-affinity receptor complex using monoclonal antibodies that recognize the beta chain, but that do not interfere with its ability to bind IL-2. Evidence is presented establishing the physical association of a novel protein of 64 kD with the beta chain in intermediate-affinity IL-2 binding sites. This molecule, termed IL-2R gamma chain, coprecipitated with beta chains prepared from cells that had been incubated with IL-2, but was undetectable in immunoprecipitates prepared in the absence of IL-2. Examination of gamma chain expression in post-IL-2 therapy NK cells, where only low levels of intermediate-affinity IL-2 binding were detectable, revealed that the gamma chain was associated with, on average, only 10-12% of the beta chains expressed on such cells. This contrasted with approximately equal levels of beta and gamma chain expression on YT cells, a cell line that has both high levels of cell surface beta chain expression and high levels of IL-2 binding. Thus, the ratio of gamma chain to beta chain present in the immunoprecipitates roughly correlated with the proportion of beta chain involved in intermediate-affinity receptor sites. This result suggests that the 64-kD gamma chain is the component responsible for regulating the affinity of IL-2 association with the beta subunit. By further defining the structural components necessary for IL-2 receptor formation, these studies provide additional insight into mechanisms whereby lymphocytes might regulate their responsiveness to IL-2.
Structure of the functional interleukin-2 receptor. Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line.
International immunology, 1989; PubMed, Homo sapiens IL2 — Homo sapiens IL2RA
ABSTRACT: The structural basis of the high affinity interleukin-2 receptor which was previously reconstituted in a cultured murine T cell line, EL4 by expressing either wild-type Tac antigen complementary DNA (cDNA) or a chimeric cDNA was characterized. The chimeric cDNA encodes a membrane portion whose extracellular portion consists of that of Tac antigen whereas transmembrane and cytoplasmic portions consists of those the human insulin beta chain. The Tac antigen/anti-Tac antibody complex was treated by chemical crosslinking reagents, purified by goat anti-mouse immunoglobulin (Ig), and was analysed by SDS-PAGE. We here demonstrated the presence in mouse EL4 transfectants of a novel membrane protein which is closely associated with the products of transfected cDNAs in the absence of interleukin-2. The protein is 75 kDa in size and is detected in cells which express high affinity interleukin-2 receptor but not in cells which only express low affinity interleukin-2 receptor. The transmembrane region and the cytoplasmic region of Tac antigen is not necessary for the formation of the complex consisting of Tac antigen and 75 kDa molecule, indicating that a murine 75 kDa molecule associates with Tac antigen extra-cellularly.
A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors.
Nature, 1987; PubMed, Homo sapiens IL2 — Homo sapiens IL2RA
ABSTRACT: Although activated human T and B lymphocytes express both high-affinity and low-affinity membrane receptors for interleukin-2 (IL-2), the structural features that distinguish these receptors have remained unresolved. The high-affinity receptors appear to mediate IL-2 induced T cell growth and internalization of IL-2, whereas no function has yet been ascribed to the low-affinity receptors. The Tac antigen is an IL-2 binding protein of relative molecular mass 55,000 (Mr 55K) that participates in the formation of both high- and low-affinity receptors. But Tac complementary DNA transfection and membrane fusion studies have suggested that additional T-cell components are required to produce high-affinity IL-2 receptors. In this study, we report the identification of a second human IL-2 binding protein that (1) has an Mr of approximately 70K, (2) lacks reactivity with the anti-Tac antibody, (3) binds IL-2 with intermediate affinity and (4) is present on the surface of resting T cells, large granular lymphocytes (natural killer cells), and certain T and B cell lines in the absence of the Tac antigen. Chemical crosslinking of 125I-labelled IL-2 bound to high-affinity IL-2 receptors produces labelling of both the p70 protein and the Tac antigen and the anti-Tac antibody blocks the crosslink detection of both of these proteins. Expression of Tac cDNA in a T cell line expressing the p70 protein, but lacking both Tac and high-affinity receptors, results in the reconstitution of high-affinity IL-2 receptors in these cells. Together, these findings suggest that the high-affinity human IL-2 receptor may be a membrane complex composed of at least the p70 protein and Tac antigen.