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

In view of the importance of the IL-2 receptors in the expression of antiallograft immunity and the currently existing controversy regarding the effect of CsA on the induction of IL-2 receptors, we explored the effect of cyclosporine on the induction of interleukin-2 receptor alpha and beta in normal human T cells. The effect of CsA on the induction of IL-2 receptors was examined at the levels of mRNA expression (with the aid of the polymerase chain reaction), protein (by SDS-PAGE analysis of chemically crosslinked 125I-IL-2 membrane protein complexes and by FACS), and function (by Scatchard analysis of 125I-IL-2 binding to T cells). The T cells were signaled with sn-1,2-dioctanoylglycerol and ionomycin or with crosslinked anti-CD3 and anti-CD2 mAbs. Our experimental design revealed that (A) CsA inhibits the induction of IL-2 receptor alpha and beta in normal human T cells, (B) the inhibitory activity is realized by a direct effect on T cells, and (C) the inhibitory activity is detectable at the pretranslational level--CsA significantly reduced the induction of mRNA encoding IL-2 receptor alpha and IL-2 receptor beta. These observations together persuasively demonstrate the ability of CsA to interrupt the emergence of IL-2 receptors on the surface of normal human T cells.
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PMID:Inhibition of interleukin 2 receptor expression in normal human T cells by cyclosporine. Demonstration at the mRNA, protein, and functional levels. 134 44

In this study we have used a new method for human recombinant IL-1 beta (rIL-1 beta) purification and investigated its immunostimulatory biological activity. The IL-1 beta gene was cloned using a novel mRNA preparation from activated human blood monocytes. The purification protocol consists of extraction and two chromatographic steps using the new Soloza cation exchange resin. The purified protein was characterized electrophoretically, by amino acid analysis and reverse phase chromatography. The protein migrated on SDS-PAGE with a molecular weight of 18.200 but demonstrated the minor presence of aggregates (dimers and trimers). Specific activity of purified rIL-1 beta in comitogenic assay on mouse thymocytes was 10(8) U/mg protein. rIL-1 beta increased in a dose dependent manner proliferation of Con A-stimulated murine thymocytes, splenocytes, PHA-stimulated human peripheral blood lymphocytes and transformed B-cell lines. Comitogenic activity depended on the degree of lymphocyte preactivation and was similar to that of natural human IL-1 beta. rIL-1 beta enhanced IL-2 production by murine spleen cells and EL-4 cell line and IL-2 receptor expression by human peripheral blood mononuclear cells. It induced PGE2 release from human blood monocytes but had no effect on human neutrophil chemotaxis, phagocytosis and respiratory burst.
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PMID:Purification and characterization of the immunostimulatory properties of recombinant human interleukin-1 beta. 187 90

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
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PMID:A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. 240 92

In a previous paper [Horuk, Huang, Covington & Newton (1987) J. Biol. Chem. 262, 16275-16278] we reported that there were fundamental differences in the biochemical properties of the interleukin-1 (IL-1) receptor between Raji and EL4 cell lines. In the present study we have investigated the basis for these differences. Kinetic studies measuring the on and off rates of IL-1 receptor binding revealed that the low-affinity IL-1-binding sites observed in Raji cells, compared with EL4 cells, result from a combination of a lower association rate and a higher dissociation rate in the Raji cells. The turnover of the Raji IL-1 receptor, measured by inhibiting protein synthesis with cycloheximide, was much faster than that of the EL4 IL-1 receptor, with a half-time of 2 h as against 5 h. Treatment of 125I-IL-1-labelled IL-1 receptors in Raji and EL4 cells with neuraminidase decreased their molecular mass by approx. 2-5 kDa as assessed by SDS/polyacrylamide-gel electrophoresis (PAGE). The covalently labelled IL-1 receptors in both cell types were sensitive to treatment with endoglycosidase F, which decreased their molecular mass on SDS/PAGE by 12-13 kDa. Incubation of Raji cells with maximally stimulating doses of IL-1 resulted in an increase in the nascent RNA levels of several genes, including the IL-2 receptor and the proto-oncogenes c-Ha-ras and c-myc.
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PMID:The interleukin-1 receptor in Raji human B-lymphoma cells. Molecular characterization and evidence for receptor-mediated activation of gene expression. 252 95

Human peripheral blood monocytes (Mo) synthesize prostaglandin E2 (PGE2) when activated with lipopolysaccharide (LPS). This production is strongly enhanced by the addition of supernatant from phytohaemagglutinin (PHA)-activated T cells. To evaluate the factor(s) responsible for this enhancement we studied the effect of several cytokines on the PGE2 metabolism. Recombinant interleukin-1 (IL-1) or recombinant IL-2 strongly enhanced PGE2 synthesis in LPS-stimulated Mo cultures, whereas recombinant interferon-gamma (IFN-gamma) partially inhibited its production. To see whether the effect of IL-2 on Mo was due to the presence of IL-2 receptor (IL-2R) on the cell surface, flow cytometric analysis and electron microscopy were used to investigate IL-2R expression in unstimulated and stimulated Mo. Stimulated, but not resting, Mo displayed the p55 IL-2R chain on their cellular surface and associated with the polyribosomes of the rough endoplasmic reticulum in the cytoplasm. This finding strongly suggested that the p55 chain of the IL-2R was synthesized by activated Mo. To confirm this result, 125I-labelled IL-2 was bound under high- and low-affinity conditions and cross-linked to Mo cultured in the presence of LPS, IFN-gamma or IL-1. The cross-linked 125I-IL-2/IL-2R complexes were analysed by SDS-PAGE. Mo cultured with LPS, IFN-gamma and IL-1 expressed the p55 protein detected by low-affinity cross-linking, whereas only LPS-stimulated Mo displayed a barely detectable band with an apparent MW of 70,000 under high-affinity binding conditions. In addition, stimulated Mo were found capable of producing the soluble form of IL-2R. Finally, LPS-activated Mo only responded to the addition of IL-2 by an increase in PGE2 production, suggesting that the function of IL-2R on activated Mo is linked to the stimulus applied.
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PMID:The expression of functional IL-2 receptor on activated macrophages depends on the stimulus applied. 266 16

Human lymphocytes respond to IL-2 with the generation of MHC-unrestricted oncolytic activity. This function has been named lymphokine-activated killing (LAK). To investigate the mechanism by which IL-2 activates and maintains LAK, we have examined the role(s) of IL-2 cell surface receptors. Removal or blockade of unstimulated lymphocytes expressing the IL-2 receptor Tac does not preclude the acquisition of LAK function. Therefore, a non-Tac IL-2 receptor was proposed to be involved in LAK generation. Using direct 125I-IL-2 binding to Tac-negative LAK precursors suggested the existence of such an alternate IL-2 receptor. Chemical crosslinking of 125I-IL-2 to Tac-depleted lymphocytes followed by SDS-PAGE determined that the size of the non-Tac-binding protein was approximately 75 kDa. Tac-negative lymphocytes activated by a limited IL-2 pulse which was insufficient for detectable Tac upregulation indicated that an initial non-Tac pathway was involved in functional differentiation. The development of lytic function, Tac upregulation, and cellular proliferation was prohibited by trypsin, a treatment shown also to eliminate 125I-IL-2 binding to Tac-negative lymphocytes. The Tac antigen, although not involved in the initial generation of LAK, is involved in the proliferative maintenance of this lytic function.
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PMID:Functional differentiation of human lymphokine-activated killing (LAK) is distinct from expansion and involves dissimilar interleukin 2 receptors. 312 71

IgG antilymphocyte antibodies preferentially reacting with phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) and an adult T cell leukemia cell line were detected in 70.6% sera from patients with systemic lupus erythematosus (SLE), using a fluorescence activated cell sorter (FACS). In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, 2 major peaks with an apparent molecular weight 60,000 to 65,000 Da and about 40,000 Da were observed in the membrane glycoprotein fractions of both PHA activated PBL and an adult T cell leukemia cell line. From the result of sequential coprecipitation analysis of SDS-PAGE between SLE serum, antiinterleukin-2 (IL-2) receptor antibody (anti-Tac antibody) and anti-Ia antibody, the reactive antigen on the activated PBL and an adult T cell leukemia cell line proved to be an identical molecule of the IL-2 receptor on these cells. The role of this autoantibody in the modulation of T cell mediated immunity in patients with SLE is discussed.
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PMID:Antibody to activated lymphocytes in patients with systemic lupus erythematosus. 312 75

Low and high affinity receptors for interleukin 2 were investigated on interleukin 2 (IL-2) receptor bearing cells by chemical cross-linking of 125I-labelled IL-2 to its receptor, or membrane proteins associated with the IL-2 binding sites. SDS-PAGE analysis of the cross-linked complexes of the murine CTLL 16 cells and human T-blasts, which bear high and low affinity IL-2 receptors, showed three distinct bands. The fastest of those three bands ran in parallel to the single band of 65-70 kDa found on the only low affinity receptor bearing mouse T-lymphoma Eb, which is thought to be one beta-chain (55 kDa IL-2 binding protein) and one IL-2. Both upper bands ran in parallel with those produced by the 2C8 clone of the NK-like cell line YT which lacks the 55 kDa binding protein and bears only a single class of receptors with an intermediate affinity. Internalisation studies using CTLL 16 cells revealed that all three bands disappeared under conditions allowing receptor internalisation. Low and high affinity binding sites of CTLL 16 cells were destroyed by trypsinisation and the IL-2 binding properties of the cells were regenerated in parallel with the reappearance of all bands. These results show in addition to the beta-chain (55 kDa binding protein) and the alpha-chain 75 kDa binding protein, an IL-2 membrane protein complex with an apparent mol. wt of 115 kDa in CTLL 16 cells. They are the first direct indication of a putative gamma-chain of the high affinity IL-2 receptor.
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PMID:The high affinity interleukin 2 receptor: evidence for three distinct polypeptide chains comprising the high affinity interleukin 2 receptor. 326 78

There is increasing evidence suggesting that the monoclonal antibodies ART-18, AMT-13 and anti-Tac recognize species-specific antigenic determinants of the interleukin-2 (IL-2) receptors of rat, mouse and human origin, respectively. In order to compare directly the molecules (glycoproteins) recognized by these antibodies, concanavalin A (ConA) activated T-lymphocytes of the respective species were surface labeled with 125I, after which the materials immunoprecipitated by the appropriate anti-IL-2 receptor antibodies were subjected to SDS-PAGE analysis. The noncross-reacting antibodies ART-18 and AMT-13 both precipitated a 50-55-kD molecule. The anti-Tac-reactive material (the putative human IL-2 receptor) is considerably different (60-65 kD) from those precipitated by antibodies ART-18 and AMT-13 (the putative rat and mouse IL-2 receptors). An indirect binding assay using the anti-mouse IL-2 receptor antibody AMT-13 showed that, after addition of ConA to spleen cell cultures, T-lymphocytes expressed IL-2 receptors before the onset of the ConA-induced DNA synthesis. The ConA-induced expression of the IL-2 receptor is apparently a transient event. IL-2 receptor bearing cells progressively lost their receptors (within 6 days) when recultured in the absence of ConA. Cells re-exposed to ConA regained IL-2 receptors. Short exposure of T-cells (thymocytes) to ConA or the nonmitogenic compound phorbol myristate acetate (PMA) is not sufficient to trigger IL-2 receptor expression. Murine thymocytes incubated with PMA for 30 min or with ConA for 4 hr (mitogen-pulsed T-cells) failed to bind the anti-IL-2 receptor antibody AMT-13 and to absorb IL-2 activity present in semipurified IL-2 preparations, but they proliferated vigorously in response to the same IL-2 preparations. The IL-2 preparations, when absorbed with thymocytes, lost: (1) the capacity to generate IL-2 receptors, and (2) the capacity to induce proliferation of mitogen-pulsed cells; but they retained the capacity to induce proliferation of T-lymphoblasts. These results suggest the existence of a factor, IL-2 receptor inducing factor (RIF), present in the IL-2 preparations. It is postulated that RIF is a prerequisite for the acquisition of IL-2 receptors and consequently for IL-2 responsiveness by lectin-activated cells.
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PMID:Studies on the interleukin-2 receptor, its generation and dynamics using monoclonal anti-interleukin-2 receptor antibodies. 644 Nov 15

Although the mouse IL-2 receptor (IL-2R) beta and gamma c subunits have been identified by molecular cloning, the biochemical identity of these subunits has not yet been established. In the present study, the mouse IL-2R was biochemically characterized from cell lines expressing normal and aberrant IL-2R. Using novel monoclonal antibodies specific for the beta or gamma c subunits, we established that the M(r) of the beta chain is 90,000-100,000 and that of the gamma c subunit is 75,000-80,000. Analysis of transfected EL4 cells that expressed alpha, gamma c, and truncated beta subunits or mutant EL4 cells, which selectively lacked cell surface gamma c, revealed that no other material migrated to a position on SDS-PAGE characteristic of IL-2/IL-2R beta and IL-2/IL-2R gamma c cross-linked complexes, respectively. Thus, the beta and gamma c subunits appear to be the sole IL-2R constituents of these IL-2 cross-linked complexes. The IL-2/IL-2R gamma c, but not the IL-2/IL-2R beta, complex exhibited enhanced mobility after SDS-polyacrylamide gel electrophoresis under nonreducing conditions, suggesting a more compact structure for gamma c as a result of intrachain disulfide bonds. The primary posttranslational modification of the mouse beta and gamma c subunits is N-linked glycosylation. These biochemical studies reconcile past uncertainties concerning the subunit composition of the mouse IL-2R and are consistent with a model of the IL-2R containing only three subunits.
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PMID:Biochemical identity and characterization of the mouse interleukin-2 receptor beta and gamma c subunits. 764 47


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