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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human high-affinity receptor for interleukin 2 (IL-2) has been proposed as being a membrane complex composed of at least two distinct polypeptide chains: p55 (alpha chain), recognized by the anti-Tac monoclonal antibody (mAb), and p75 (beta chain), both of which are capable of binding IL-2. Whereas the alpha chain itself has been shown to be nonfunctional, the beta chain appears to be pivotal in the IL-2 signal transduction, although the beta chain is otherwise poorly characterized. Three beta chain-specific mAbs, designated Mik-beta 1, -beta 2, and -beta 3, were developed. Mik-beta 1 and -beta 2 completely inhibited the IL-2 binding to the beta chain, whereas Mik-beta 3 immunoprecipitated the beta chain crosslinked with 125I-labeled IL-2. The beta chain immunoprecipitated by these mAbs was revealed to have a Mr of 68,000-72,000. High-affinity IL-2 binding was completely abolished by Mik-beta 1. Although IL-2-dependent T-cell growth at high IL-2 concentrations was not inhibited by the anti-Tac, it was almost completely inhibited by Mik-beta 1 in the presence of the anti-Tac. These results clearly indicate that the beta chain is an indispensable component to the high-affinity IL-2 receptor and is responsible for the IL-2 signal transduction. The beta chain was found to be constitutively expressed without the alpha chain on the surface of peripheral blood Leu-19+ natural killer cells.
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PMID:Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. 246 93

The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107. 246 50

In this study, we describe a new methodology to detect and quantify lymphokine receptors, using interleukin-2 as a prototype. Human recombinant interleukin-2 (IL-2) was conjugated to fluorescein isothiocyanate. Binding of fluoresceinated IL-2 to different cell types was assessed by flow cytometry analysis, on a FACS 440 calibrated using fluoresceinated Sephadex G-25 beads. This calibration procedure allowed us to quantify the actual number of binding sites for IL-2. Fluoresceinated IL-2 did not bind to normal resting T cells, whereas a highly significant binding was observed on PHA-activated human T cells. The binding was inhibited by an excess of unlabeled IL-2 and by an excess of anti-IL-2 receptor p55 antibodies (anti-TAC). Dose curves of IL-2 showed a two plateau saturation, the first plateau corresponding to the saturation of high affinity binding sites, as assessed by correlation with the biological activity on IL-2-dependent T cells. Among the cell types tested, fluoresceinated IL-2 bound to IL-2-dependent mouse T cells (the binding in that case was not inhibited by anti-IL-2 receptor p55 antibodies), and to different p70 expressing cell lines or normal cells (MLA 144, normal large granular lymphocytes). Taken together, these results indicate that fluoresceinated IL-2 can be used to detect high as well as low affinity IL-2 binding sites.
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PMID:Detection of low and high affinity binding sites with fluoresceinated human recombinant interleukin-2. 249 69

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

By interaction with monocytes, interleukin-2 (IL-2) suppressed natural killer (NK) cell cytotoxicity (NKCC) of human, Percoll-fractionated, low-density mononuclear cells. The NK-suppressive effect of IL-2 was independent of de novo formation of prostaglandins or protein since it was unaffected by treatment with indomethacin and cycloheximide, respectively. A monoclonal antibody to the p55 (beta) moiety of the IL-2 receptor (anti-Tac/anti-CD25) blocked IL-2-induced NKCC suppression but did not affect the NK-enhancing effect of the lymphokine. We conclude that IL-2 exerts a monocyte-dependent, IL-2 beta-receptor mediated suppressive influence on human NK cells.
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PMID:Interleukin-2 can induce suppression of human natural killer cell cytotoxicity. 250 16

The high-affinity receptor for interleukin-2 (IL-2) is composed of two distinct subunits with molecular weights of 55,000 and 75,000 (p55 and p75). While the presence of the high-affinity receptor requires the simultaneous expression of p55 and p75, these subunits can also be expressed independently, resulting in IL-2 receptors with low and intermediate affinities, respectively. IL-2 can induce proliferation in cells expressing either the intermediate affinity p75 receptor or the p55.p75 high-affinity complex, suggesting that p75 is responsible for signal transduction. We have previously shown that signal transduction by the high-affinity IL-2 receptor involves the activation of a tyrosine protein kinase. In order to evaluate the role of p75 in the activation of this kinase we assessed the ability of IL-2 to induce the activation of a tyrosine protein kinase in the human leukemic cell lines Hut 78 and YT. These cells express p75 as the predominant IL-2 receptor. IL-2-dependent tyrosine phosphorylation was observed in both cell lines and the concentrations of IL-2 needed to stimulate this phosphorylation were similar to that required for binding to the p75 receptor. Antibodies that inhibit binding of IL-2 to p55 had no effect on the IL-2-induced tyrosine phosphorylations in YT cells, while antibodies that block the binding of IL-2 to p75 completely inhibited the phosphorylations. These results demonstrate that the signaling capacity for the IL-2-induced tyrosine phosphorylation resides in the p75 receptor.
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PMID:The 75,000-dalton interleukin-2 receptor transmits a signal for the activation of a tyrosine protein kinase. 251 Nov 97

Interleukin-2 (IL-2) plays an essential role in the clonal expansion of antigen-activated T lymphocytes (T cells). In fact, the expression of both IL-2 and IL-2 receptor (IL-2R, p55, CD25) genes is transiently induced upon T cell activation through the interaction of antigen/major histocompatibility complex (MHC) and T cell receptor complex. To elucidate the mechanism(s) of the induced gene expression for IL-2 and IL-2R, we have investigated for the presence of potential transcription factors that specifically interact with regulatory cis-elements. Here, we demonstrate that one such factor mediates the induced expression of both genes. Interestingly, the recognition sequences by this factor are significantly diverse in these two genes and are related to those of immunoglobulin (Ig) kappa chain and MHC class I genes. We provide evidence that this factor indeed binds to the IL-2, IL-2R, and Ig sequence elements with different affinities, thereby affecting the magnitude of gene expression. Interestingly, this factor also binds to other cytokine genes, such as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and HIV-1 and HTLV-1 LTR sequences.
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PMID:Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes. 251 55

The low affinity IgE receptors (Fc epsilon RII/CD23) homologous to animal lectins have the unique property of cleaving-off the extracytoplasmic portion as the soluble form (IgE binding factor; IgE-BF). Molecular analysis using Fc epsilon RII/CD23 cDNA proved that Fc epsilon RII is not unique to B lymphocytes but is expressed on a variety of cell lineages including T lymphocytes, macrophages and eosinophils. In these cell types, IL-4 is a general inducer of this molecule while IFN-gamma down-regulates B cell Fc epsilon RII/CD23 and up-regulates Fc epsilon RII/CD23 on macrophage and eosinophil cell lines. As predicted by the expression of Fc epsilon RII/CD23 in some HTLV-1(+) T cell lines, Fc epsilon RII/CD23 proved to be induced on normal peripheral T lymphocytes by IL-4 or IL-2 in the presence of additional permissive signals. As indicated by IL-2-dependent Fc epsilon RII/CD23 induction, there is an interesting bilateral co-regulation between Fc epsilon RII/CD23 and the 55 kDa chain of the IL-2 receptor complex with Tac antigen (IL-2R/p55(Tac]. Triggering of Fc epsilon RII/CD23 resulted in the enhanced expression of IL-2R/p55(Tac), whereas IL-2 enhanced the expression of Fc epsilon RII/CD23 in some systems. It is suggested that the triggering of cell surface Fc epsilon RII/CD23 by natural ligands is effectively buffered by soluble Fc epsilon RII/CD23 (IgE-BF).
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PMID:Low affinity IgE receptors: regulation and functional roles in cell activation. 253 50

The cell-surface receptor for interleukin-2 (IL-2) consists of two unlinked polypeptides of 55 and 75 kDa (p55, p75). The monoclonal antibody antiTac binds to p55 alone. We show here that the binding of either IL-2 or antiTac to the surface of T lymphocytes triggered the generation of cAMP. Reagents which activate adenyl cyclase by stimulation of its guanine nucleotide-binding protein (Gs) also stimulated increases in cAMP. All of the above reagents, and cAMP itself, stimulated the turnover of phosphate residues bound to serine and threonine residues of an 85 kDa protein. The data provide evidence that the binding of ligands to the p55 component of the IL-2 receptor generates a biochemical signal by the stimulation of adenyl cyclase via Gs, and that the consequent generation of cAMP and activation of cAMP-dependent protein kinase modulates the turnover of p85-bound phosphate groups.
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PMID:The binding of ligands to the 55 kDa component of the interleukin-2 receptor triggers increased turnover of phosphate bound to an 85 kDa protein. Evidence for the role of cyclic AMP. 253 32

The leukocyte-common antigen (L-CA) is a family of large molecular weight glycoproteins uniquely expressed on the surface of all nucleated cells of hematopoietic origin. The glycoprotein consists of a heavily glycosylated exterior domain, a single membrane spanning region, and a large cytoplasmic domain that contains tyrosine phosphatase activity. To investigate the function of this family, we generated T cell clones that lacked L-CA (L-CA-). The expression of the alpha beta T cell receptor, CD3, CD4, IL-2 receptor (p55), LFA-1, Thy-1, and Pgp-1 (CD44) was normal. The L-CA- T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2. An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen.
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PMID:Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. 255 Jan 43


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