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)

The characteristics of a novel T lineage-specific activation antigen, termed TLiSA1, are described. The antigen was detected with a mouse monoclonal antibody, LeoA1, that was raised against activated human T cells generated in mixed lymphocyte culture (MLC). The antigen became strongly expressed on T cells 48-72 h after stimulation with phytohemagglutinin, and retained expression on MLC-activated T cells after 10 d of culture. The antigen was absent from a range of human T, B, myeloid, fibroblast, and tumour cell lines, but was present on the surface of the interleukin 2 (IL-2)-dependent gibbon cell line MLA-144. Analysis of the antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of immunoprecipitates obtained from activated human T cells demonstrated a broad band in the region of 70 kD, whereas precipitates obtained from MLA-144 revealed a single narrow band of 95 kD. The molecule was expressed with a maximum density of 66,000 copies per cell on the surface of MLC-activated T cell blasts, as assessed by Scatchard analysis. TLiSA1 was distinguished from the IL-2 receptor bound by the anti-Tac monoclonal antibody by demonstrating that the antigens did not comodulate or coprecipitate, and by constructing an IL-2-independent human T X T hybrid that expressed the TLiSA1 but not the Tac antigen. MLC with B lymphoblasts was used to generate cytotoxic T lymphocytes (CTL) specific for the stimulating cell, and anomalous killer (AK) cells able to kill melanoma target cells. The presence of LeoA1 or F(ab')2 fragments of the antibody from the beginning of coculture did not affect proliferation in these cultures, but did inhibit the induction of both CTL and AK cells from their precursors. This inhibition of differentiation by LeoA1 was confirmed under conditions of limiting dilution, where it was shown that the antibody reduced the frequency of CTL produced, and greatly (fourfold) reduced the frequency of AK cells generated from their precursors. We discuss the possibility that human CTL may express a differentiation factor receptor that is distinct from the receptor for IL-2.
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PMID:TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors. 258 Sep 33

The expression of the interleukin-2 (IL-2) receptor was studied in neoplastic cells derived from acute leukemias, T-cell lymphoblastic lymphomas, peripheral T-cell lymphomas, chronic lymphocytic leukemias, well-differentiated lymphocytic lymphomas, and established cell lines by both flow cytometric analysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) after affinity crosslinking of radiolabeled IL-2. Cells from most acute leukemias (19 of 22), irrespective of their subtype (T, common or nonlymphoid leukemias), as well as T-cell lymphoblastic lymphomas and peripheral T-cell lymphomas expressed only the p70-75 beta subunit of the IL-2 receptor. Cells from the more mature B-cell neoplasms, chronic lymphocytic leukemia, and well-differentiated lymphocytic lymphoma, expressed predominantly alpha beta IL-2 receptors (11 of 14). In contrast to these results, most cell lines established from hematopoietic malignancies do not express either chain of the IL-2 receptor. Further studies are necessary to determine the exact function of the IL-2R p70-75 beta subunit in immature hematopoietic cells, but its wide distribution throughout the hematopoietic system suggests that IL-2 may play a role in the early stages of hematopoiesis.
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PMID:Expression of interleukin-2 receptor beta subunit in hematopoietic malignancies. 265 67

Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70-75 as determined by [125I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70-75) and Tac (p55) peptides by [125I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.
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PMID:Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes. 278 85

Human recombinant interleukin-2 (IL-2) and a soluble recombinant form of the human p55 (Tac antigen) component of the IL-2 receptor (IL-2R) have been cocrystallized in 1.7-1.8 M ammonium sulfate, in the pH range 7.0-8.2. Variously glycosylated forms of both receptor and ligand can be cocrystallized under those conditions. The best crystals of the putative receptor-ligand complex involve the enzymatically desialylated receptor and unglycosylated IL-2. These crystals belong to the trigonal space group P3(1)2(1) or its enantiomorph, with unit cell dimensions a = b = 91 A and c = 119 A, and diffract to 3.5 A resolution. There is one receptor-ligand complex asymmetric unit, with a Matthews coefficient of 2.7, assuming the presence of one IL-2 molecule-receptor molecule. Interestingly, in addition to IL-2 (Mr = 14,000), the p55 IL-2 receptor (Mr = 44,000) and two fragments of the receptor, of apparent Mr = 35,000 and 25,000, respectively, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the crystals are enriched in a reducible dimeric form of the desialylated receptor (apparent Mr = 90,000), as compared with protein solution from which the crystals grow. The overall amino acid content in the crystals is consistent with a 1:1 ratio of receptor to ligand. A native data set has been collected on a multiwire area detector and the search for suitable heavy atom derivatives is in progress.
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PMID:Crystallization and preliminary X-ray diffraction studies of a complex between interleukin-2 and a soluble form of the p55 component of the high affinity interleukin-2 receptor. 278 21

Ca2+/phospholipid-dependent kinase activity (C-kinase) plays an important second messenger role in T lymphocyte responses initiated by the cluster of differentiation (CD3) complex and presumably also lectinic receptors. During treatment with submitogenic or mitogenic amounts of phytohemagglutinin, as well as with anti-CD3 monoclonal antibody and 12-O-tetradecanoyl 13-phorbol acetate, the enzyme was intracellularly redistributed between the cytosol and the surface membrane. Submitogenic amounts of lectin and anti-CD3 were ineffective in inducing proliferation unless exogenous interleukin 2 (IL-2) was supplied, implying that even though IL-2 receptors were expressed, additional signals were required for IL-2 production. This would also indicate that there is a direct relationship between activation of C-kinase and expression of IL-2 receptors. The importance of C-kinase was further substantiated by the ability of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H7), a potent inhibitor of this enzyme, to interfere with IL-2 receptor expression and cellular [methyl-3H]thymidine uptake during primary activation. The drug concentration at which these cellular responses were inhibited by 50% was about the same as that which decreased c-kinase activity by 50% in vitro. H7 also prevented anti-CD3-induced translocation in intact cells. This effect may be related to competition with the phosphatidylserine binding site, which is important for membrane attachment. This drug apparently also interferes with the active center of the enzyme as demonstrated by its ability to inhibit Ca2+/phospholipid-independent phosphorylation of protamine sulfate. This additional mode of inhibition may be important in suppressing intact cell responses under circumstances during which the enzyme displacement to the membrane is nonphysiologic in nature, e.g., during treatment with 12-O-tetradecanoyl 13-phorbol acetate.
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PMID:Inhibition of antibodies to CD3 surface antigen and phytohemagglutinin-mediated T cellular responses by inhibiting Ca2+/phospholipid-dependent protein kinase activity with the aid of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride. 282 Nov 9

We studied the expression of the interleukin-2 (IL-2) receptor and the proliferative response to exogenous IL-2 of peripheral blood leukemic cells from patients with adult T cell leukemia (ATL) in order to see whether IL-2 receptor expressed on ATL cells is different from normal IL-2 receptor and whether it plays a role in the neoplastic growth in ATL. Peripheral blood leukemic cells from 42 patients with ATL examined expressed IL-2 receptors that were detected by anti-Tac monoclonal antibody when examined immediately after the separation of cells or after the culture for 24 or 48 h. The number of anti-Tac binding sites ranged from 3,100 to 11,400 in fresh cells and from 3,600 to 96,000/cell in short-term cultured leukemic cells, whereas phytohemagglutinin-P (PHA-P)-stimulated normal T cells exhibited 6,900-35,000 anti-Tac binding sites per cell. ATL-derived and human T cell leukemia/lymphoma virus, type I (HTLV-I)-infected cell lines such as MT-1 and Hut102 expressed a much higher number of anti-Tac binding sites. Leukemic cells from 15 patients with ATL examined showed no or very poor proliferative response to various concentrations of immunoaffinity-purified IL-2, although they expressed Tac antigen (Ag). Radiolabeled IL-2 binding experiments demonstrated that ATL leukemic cells could bind IL-2, and they expressed both high and low affinity IL-2 receptors, although the number of high affinity IL-2 receptor was much less than that of low affinity IL-2 receptor and that of anti-Tac binding sites. In contrast, leukemic T cells from a patient with T cell chronic lymphocytic leukemia (CLL), in whom HTLV-I infection was not demonstrated, responded as well as PHA-P-stimulated normal T cells, and their IL-2 receptors, unlike ATL cells, were modulated (down regulated) by anti-Tac antibody. No differences were noted between ATL cells and normal activated T cells in one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of the IL-2 receptor. Thus, leukemic cells in ATL spontaneously and continuously express IL-2 receptor, which appears to be abnormally regulated and unresponsive to IL-2. These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells.
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PMID:Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. 299 59

Three previously selected monoclonal antibodies (mAb) directed against the clonotypic structure of a variant (termed JA3) of the interleukin 2 (IL-2)-producing Jurkat leukemia cell line (anti-JTi1-3 mAb) were found to induce an adherent cell-dependent proliferation of peripheral blood T cells in 20 different donors. Unlike the early cell proliferation induced by anti-T3 mAb, anti-JTi mAb-induced proliferation was detectable at day 5-6 of culture and reached peak levels at day 7-9. Less than 1% JTi+ cells were consistently detected in the starting peripheral blood lymphocytes or in control cultures in which cells were stimulated with anti-T3, phytohemagglutinin, or allogeneic cells. However, JTi+ cells were found in increasing proportions after culture with anti-JTi mAb and they were mostly represented by large blast cells expressing either the T4 or the T8 antigen, together with typical activation antigens including HLA-DR, IL-2 receptor, and 4F2. Immunoprecipitation experiments and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that anti-JTi-reactive molecules present on antibody-stimulated lymphocytes or on JA3 cells were similar, disulphide-linked heterodimeric structures.
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PMID:Anticlonotypic monoclonal antibodies induce proliferation of clonotype-positive T cells in peripheral blood human T lymphocytes. Evidence for a phenotypic (T4/T8) heterogeneity of the clonotype-positive proliferating cells. 387 4

The role of the Legionella pneumophila protease in the pathogenesis of Legionnaires' disease is unclear. In this study, we assessed the effect of purified protease preparations on human recombinant interleukin-2 (IL-2), the IL-2 receptor, and several additional human T-cell surface proteins to determine whether protease contributes to the virulence of L. pneumophila by interfering with human T-cell activation and function. IL-2-induced proliferation of CTLL-2 cells was inhibited by coincubation with protease (10 to 100 U/ml). Protease at concentrations of > or = 10 U/ml cleaved human recombinant IL-2 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reaction mixtures containing 125I-labeled IL-2 and protease. Protease treatment of activated human T cells did not inhibit binding of a monoclonal antibody directed against the alpha subunit of the IL-2 receptor and did not interfere with binding of IL-2 to IL-2 receptors on the lymphocytes. Treatment of blood mononuclear cells or activated T cells with protease (50 U/ml) inhibited the binding of a monoclonal antibody directed against CD4. In contrast, protease treatment did not inhibit the binding of antibodies against CD3, CD8, class II major histocompatibility complex, and the transferrin receptor. Heat inactivation (65 degrees C for 20 min) of the protease or treatment with the metal chelator EDTA ablated the inhibitory effect of the protease. The ability of the protease to degrade IL-2 and cleave CD4 on human T cells suggests that protease may contribute to the pathogenesis of Legionnaires' disease by impeding T-cell activation and immune function.
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PMID:Legionella pneumophila protease inactivates interleukin-2 and cleaves CD4 on human T cells. 833 71

We previously reported the generation and characterization of a panel of CD4(+) autoreactive T cell clones that suppress development of autoimmune diabetes in non-obese diabetic (NOD) mice. We showed that the protective capacity of the T cell clones correlated with secretion of an activity that potently inhibits allogeneic mixed lymphocyte reaction (allo-MLR). In this report, we describe the biological characteristics of the allo-MLR inhibitory activity (MLR-IA, short for mixed lymphocyte reaction inhibitory activity) secreted by the protective T cell clone, NOD-5. MLR-IA has little effect on initiation of proliferation in an allo-MLR, but it potently inhibits the maintenance and amplification of the proliferative response. MLR-IA is also capable of inhibiting concanavalin A (Con A) stimulated splenic responder T cell proliferation. MLR-IA is reversible in vitro and is not restricted by MHC class I or II proteins. MLR-IA does not affect IL-2 receptor expression of responding T cells and has no effect on IL-2-dependent proliferation of CTLL-20 T cells. Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation. MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma, suggestive of a novel activity. MLR-IA is ammonium sulfate precipitable, sensitive to protease digestion and is destroyed by boiling, indicating that a protein moiety is part of its active structure. Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice.
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PMID:Biological characteristics of an immunoregulatory activity secreted by an autoreactive CD4+ T cell clone that suppresses autoimmune diabetes in non-obese diabetic mice. 867 56

We previously showed the median duration of positive patch test reactions to nickel sulfate (5% pet.) was 9 days, and defined as long-lasting (LLAPTR) the 14.3% of reactions that persisted for 17 days or longer. The pathomechanisms of LLAPTR are unclear, but may involve either localized antigen persistence or abnormal downregulation of the cellular immune response. In this study, we compared (a) the nickel concentration and (b) the immunocytochemical nature of the local immune reaction, between biopsies from LLAPTR (n = 8) and normally resolving allergic patch test reactions (NRAPTR) (n = 8) to nickel sulfate. The concentration of nickel in LLAPTR (median 0.56 microgram/g, range 0.25-3.87 micrograms/g, mean 0.83 microgram/g, 95% CI 0.35-1.31) and NRAPTR (median 0.58 microgram/g, range 0.2-1.85 micrograms/g, mean 0.88 microgram/g, 95% CI 0.02-1.74) was similar. Activated T lymphocytes, expressing surface IL-2 receptor, HLA DR, DR alpha 1, DP, DQ, and CD2 > CD8 > CD4 antigens, were seen throughout the dermis and occasionally infiltrating the suprabasal layer of the epidermis in all biopsies. CD1 and HLA DR, DR alpha 1, DP, and DQ-expressing Langerhans cells were present throughout the epidermis and occasionally seen in the papillary dermis. HLA DR, DR alpha 1, DP, and DQ antigen expression were also seen on the surface of non-dendritic cells in the epidermis (probably either keratinocytes or T lymphocytes) and vascular endothelial cells in the papillary dermis. There were no significant qualitative or quantitative differences in the immunocytochemical nature of the localized immune reaction between LLAPTR and NRAPTR. These findings suggest that the pathomechanism of LLAPTR to nickel sulfate is unlikely to be explained simply on the basis of nickel concentration or the nature of the localized immune reaction at the patch test site.
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PMID:Long-lasting allergic patch test reactions to nickel sulfate: analysis by nickel quantification and immunocytochemistry. 868 35


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