Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the action of a chimeric protein, IL-2-PE40, on the development of a T cell-mediated disease of the central nervous system with numerous similarities to multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). EAE is caused by IL-2 receptor-bearing T cells specific for myelin basic protein (BP). We report here that the treatment of Lewis rats with IL-2-PE40 delayed and shortened the course of EAE induced by BP in adjuvant and dramatically prevented EAE mediated by anti-myelin basic protein T line cells. The absence of paralytic signs, the absence of cell infiltration in the central nervous system, and the abatement of cellular immunity to myelin basic protein in the treated rats are direct consequences of the specific mechanism of action of IL-2-PE40. Our data support the notion that IL-2-PE40 may be efficient as an immunosuppressive agent for those disorders in which activated T cells play a crucial role.
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PMID:Immunospecific suppression of encephalitogenic-activated T lymphocytes by chimeric cytotoxin IL-2-PE40. 170 63

Recombinant technology has facilitated the production of two soluble forms of human p55 interleukin-2 receptor (IL-2R) in Chinese hamster ovary cells. We have developed a ligand-affinity method for the medium-scale purification of these two soluble forms of the IL-2R, based on the biochemical interactions between the matrix-bound ligand (interleukin-2) and its soluble receptor. The affinity-purified IL-2R is further purified by anion-exchange chromatography followed by gel filtration. This method has provided enough highly pure IL-2R for structure and function studies and for use in practical applications such as high-flux drug-screening assays. The purified IL-2R subsequently has been immobilized on silica gel and employed for the purification of recombinant IL-2. Receptor-affinity-chromatography-purified IL-2 contains only a highly active monomeric form of the lymphokine, in contrast to immunoaffinity chromatography where several molecular forms of IL-2 with varying degrees of biologic activity are recovered. Receptor-affinity chromatography has been successfully applied to the purification of several mutant IL-2 as well as an IL-2-Pseudomonas exotoxin (IL2-PE40) fusion protein that is a 54.5-kDa chimeric protein in which the cell recognition domain is replaced by IL-2. The IL-2-PE40 is a potential cytotoxic agent for cells bearing the IL-2 receptor.
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PMID:Purification of the IL-2 receptor (TAC) by ligand-affinity chromatography and utilization of the immobilized receptor for receptor-affinity chromatography (RAC) purification of IL-2, mutant IL-2, and IL-2 fusion proteins. 235 48

IL-2-PE40 is a chimeric protein composed of human interleukin 2 (IL-2) genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. IL-2-PE40, which is extremely cytotoxic to IL-2 receptor-positive cells, was examined for its ability to prevent graft rejection in mice in which activation of T cells is prominent. We demonstrate that intraperitoneally administered IL-2-PE40 specifically and significantly prolongs the survival of vascularized heart allografts in mice. The chimeric toxin, IL-2-PE40, offers an alternative approach to the treatment of autoimmune diseases and transplant rejection in humans.
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PMID:Cardiac allograft survival in mice treated with IL-2-PE40. 264 40

A cDNA clone for human interleukin 2 (IL-2) has been fused to the 5' end of a modified Pseudomonas exotoxin (PE) gene that lacks the sequences encoding the cell recognition domain. The chimeric protein IL-2-PE40 was produced in Escherichia coli. It was extremely toxic to IL-2 receptor-positive cells but had no measurable effect on cells lacking the IL-2 receptor. IL-2-PE40 might be a useful cytotoxic agent in the treatment of diseases involving IL-2 receptor-positive cells and in the treatment of allograft rejection.
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PMID:Cytotoxic activity of an interleukin 2-Pseudomonas exotoxin chimeric protein produced in Escherichia coli. 312 99

To study the structural basis of ligand-induced receptor-mediated internalization of interleukin-2 (IL-2), a strategy has been developed to generate variant T cells that are deficient in internalization of this cytokine. IL-2 receptor (IL-2R) alpha- and beta-bearing EL4 cells, that express high-affinity IL-2R and internalize IL-2, were treated with low doses of IL-2-Pseudomonas exotoxin chimeric protein (IL-2-PE40). This treatment resulted in isolation of a variant (CX1) that was unable to express high-affinity IL-2R or internalize IL-2. Transfection of CX1 with the IL-2R beta cDNA led to surface expression of IL-2R beta and high-affinity IL-2R as well as the ability to internalize IL-2. This finding indicates that the absence of the beta subunit was the sole defect in CX1 responsible for its failure to internalize IL-2. By transfecting CX1 with mutated beta cDNA, several CX1 transfectants were produced that expressed a beta-subunit that lacked all amino acids of the intracytoplasmic region. These transfectants expressed high-affinity IL-2R and internalized IL-2 at a rate comparable to cells expressing wild-type beta-chain. These results demonstrate that internalization of IL-2 is independent of any signals contained in the intracytoplasmic tail of the beta subunit and raise the possibility that such signals may be entirely contained within the gamma subunit.
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PMID:Selection of internalization-deficient cells by interleukin-2-Pseudomonas exotoxin chimeric protein: the cytoplasmic domain of the interleukin-2 receptor beta chain does not contribute to internalization of interleukin-2. 825 33

It has recently been shown that chimeric toxin composed of IL2 fused tp PE40, a mutant form of Pseudomonas Exotoxin A devoid of its native cell recognition and binding domain was cytotoxic to IL2 receptor bearing cells. We here amplified the gene IL-2 (60), which codes for the N-terminal 1-60 amino acids of human IL-2 by PCR. After that, we fused it to PE40 and the new chimeric protein IL-2(60)-PE40 was expressed in E. coli. SDS-PAGE revealed that IL-2(60)-PE40 chimeric protein accounts for more than 18% of total cell proteins. As the region IL-2 binds with its receptor was defined in the N-terminal residues 8-54 of IL-2, such fusion proteins will have the same activity with IL-2-PE40. Following primary purification, IL-2(60)-PE40 was shown to be very toxic to IL-2 receptor-positive cells but non measurable effect on the cells lacking IL-2 receptors. Such a structure has not been reported by now. The fusion protein is useful for suppressing the immune response in cases of rejection of allografts and organ transplants and as therapeutic agents for the treatment of IL-2 receptor related diseases such as autoimmune disease, ATL (adult T-cell leukemia), et al.
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PMID:Cloning and expression of the gene coding for IL-2(60)-PE40, a molecular targeted protein. 858 Apr 81

Interleukin-2 (IL-2) plays a pivotal role in the cellular and humoral immune responses directed against foreign antigens. We characterized the in vitro and in vivo properties of a chimeric protein consisting of mouse IL-2 fused to the mouse IgG2b Fc domains. This fusion protein binds to IL-2 and Fc receptors and supports IL-2-dependent cell proliferation but does not mediate lysis of IL-2 receptor-positive cells in the presence of murine complement in vitro. However, in vivo the IL2-IgG2b fusion protein suppresses both cellular and humoral immune responses after immunization with sheep erythrocytes. Surprisingly, delayed hypersensitivity is inhibited despite a dramatic increase of splenic CD3+ and NK1.1+ lymphocytes, indicating that altered homing of IL2-IgG2b-activated lymphocytes rather than cytolysis prevents these cells from accumulating in areas of inflammation. Although in vitro the IL2-IgG2b fusion protein does not alter proliferation of B cells in response to mitogenic stimulation, IgM production in response to sheep erythrocytes is profoundly inhibited in mice treated with the IL2-IgG2b fusion protein. Since no side effects are observed, the IL2-IgG2b fusion protein may expand the therapeutic repertoire of reagents used for the treatment of allograft rejection and autoimmune diseases.
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PMID:Suppression of cell-mediated and humoral immune responses by an interleukin-2-immunoglobulin fusion protein in mice. 863 31

The pokeweed antiviral protein (PAP) has already been used to chemically construct immunotoxins. Here we tested the recombinant approach for the production of PAP-containing cytotoxic fusion-proteins. A cDNA encoding a mutated PAP (PAP9), which is expressed at high levels in bacteria, was fused to human interleukin-2 (IL-2) cDNA. The resulting PAP9-IL-2 protein was as active as the free PAP9 in inhibiting an eukaryotic cell-free translation system. Only the chimeric protein desaminated the 28S rRNA and inhibited translation of the CTLL-2 cell line which expresses the IL-2 receptor. These results show that PAP is a suitable toxin for the production of recombinant immunotoxins.
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PMID:Expression and activity of a recombinant chimeric protein composed of pokeweed antiviral protein and of human interleukin-2. 901 57

Interleukin-2 (IL-2) is a pluripotent cytokine which plays a crucial role in the immune system response. Although the IL-2/IL-2 receptor (IL-2R) system has been well characterized in cells of the T lineage it is less known in B lymphocytes. The authors therefore studied the expression of the IL-2R alpha, beta and gamma subunits in human B-cell lines at different stages of maturation, by the polymerase chain reaction technique. The authors found that the alpha and beta subunits are expressed in the final stages of B-cell lineage maturation, whereas the gamma subunit is constitutively expressed during B-lymphocyte differentiation. The results indicate that the IL-2/IL-2R system, most probably, does not have a role in the early stages of B-cell differentiation, but may be involved only in the final stages of B-cell lineage ontogeny. Moreover, the ability of the different forms of IL-2R to internalize the IL-2 ligand was investigated, using the chimeric protein IL-2-PE66(4Glu). Cell lines bearing the alphagamma, betagamma and alpha betagamma forms of IL-2R were inhibited by the chimeric protein, while those bearing the gamma subunit alone did not respond to the chimera. Thus, internalization of IL-2 is most likely mediated via the alphagamma form of the IL-2R, as shown here for the first time, as well as through the betagamma and alpha betagamma IL-2R forms. However, IL-2 cannot be internalized through the IL-2R gamma subunit alone.
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PMID:Interleukin-2 (IL-2) receptor alpha, beta and gamma subunit expression as a function of B-cell lineage ontogeny: the use of IL-2-PE66(4Glu) to characterize internalization via IL-2 receptor subunits. 958 93

We have developed a method that enables us to isolate cDNAs of putative membrane proteins. The system is designed to isolate a cDNA which can provide the transmembrane domain to the extracellular part of the IL-2 receptor alpha chain. We constructed a p18Mac vector by putting part of the IL-2 receptor alpha chain cDNA that encoded its signal sequence and extracellular domain, a cDNA cloning site and a poly(A) additional signal after a strong promoter SRalpha. If a cloned cDNA provides a transmembrane domain in-frame, the extracellular domain of the IL-2 receptor alpha chain will be expressed on the surface of the transfected cells. Otherwise, the chimeric protein will be either secreted or retained inside the transfected cells. We made a cDNA library using p18Mac and screened for cDNA clones which allowed the expression of the extracellular domain of the IL-2 receptor alpha chain on the cell surface. Of the 2000 clones screened, 5 clones were scored as positive. Partial sequence analysis revealed that one clone encoded the amyloid precursor protein, two others encoded mitochondrial proteins and the rest were new. These results suggest the system is effective in isolating cDNAs encoding putative membrane proteins.
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PMID:Transmembrane-domain trapping: a novel method for isolation of cDNAs encoding putative membrane proteins. 973 13


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