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)

A female patient with an unusual lymphoproliferative disease associated with marked neutropenia has been observed for 36 months. The expanded cell population consists of large lymphocytes, many of which contain large azurophilic granules with acid phosphatase activity. These cells were T3, T8, T11 and Leu 11 positive but lacked the M1, T10, IL-2 receptor and HLA.DR antigens. The majority of these cells (60-70%) were also Leu 7 (HNK-1) positive. Strong natural killer (NK) activity was found in both the Leu 7 positive and negative cell populations. This cytotoxic activity was inhibited by monoclonal antibodies known to inhibit NK activity but was unaffected by antibodies which block T cell and T/NK cell cytotoxicity. Further functional analysis indicated that these cells suppressed normal T cell responses to mitogens, MLC responses and PWM induced B cell immunoglobulin synthesis. No effect on bone marrow progenitor cell growth was demonstrated. Antibody dependent cellular cytotoxic (ADCC) activity was barely detectable despite the presence of the Leu 11 antigen. Southern blot DNA analysis demonstrated clonal rearrangement of the T cell receptor beta gene thereby confirming that this variant of T gamma lymphoproliferative disease was a neoplastic condition.
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PMID:Functional analysis of a clonal expansion of Leu 11 positive NK active lymphoid cells. 295 59

We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.
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PMID:Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells. 296 15

A recombinant amphotropic retrovirus was used to introduce the protein-coding region of the IL-2 receptor cDNA derived from HUT-102 cells into human CEM leukemic T-cells that lack these receptors. CEM T-cells that contained the virus expressed functional IL-2 receptors that transiently mediated five- to tenfold increases in [3H]thymidine incorporation following the addition of picomolar quantities of IL-2. Although IL-2 responsiveness was subsequently lost, it could be reinduced by cellular activation with the OKT11 monoclonal antibody. This phenotype also proved unstable with progressive time in culture. Despite the loss of IL-2 responsiveness, the infected CEM T-cells continued to express Tac antigen and displayed 50 to 200 high-affinity IL-2 receptors per cell that bound IL-2 with a dissociation constant of 4.3 pM. This affinity is fully equivalent to that detected on activated normal T-cells (2 to 50 pM). The apparent molecular size of the Tac antigen on these cells (55,000 to 60,000 daltons) was comparable to that on normal activated T-cells but 5000 daltons larger than the aberrant IL-2 receptors on HUT-102 cells. These data demonstrate that expression of a human IL-2 receptor cDNA in human T-cells results in high-affinity IL-2 receptor display that transiently imparts an IL-2 responsive state of growth. These results also raise the possibility that the T11 surface receptor may play an important regulatory role in high-affinity IL-2 receptor expression.
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PMID:Reconstitution of high affinity IL-2 receptor expression in a human T-cell line using a retroviral cDNA expression vector. 311 93

The present knowledge of the inflammatory reaction occurring in situ during hepatitis B favors a T cell-dependent MHC-restricted immune response. However, the reports in the literature are primarily based on the application of monoclonal antibodies directed at different lymphocyte subsets which discern only lymphocytic phenotypes and do not reflect the actual situation adequately. Therefore, we investigated the liver biopsies of patients with hepatitis B (28 patients) and non-A, non-B (21 patients) by immunoelectron microscopy with monoclonal antibodies directed at lymphocyte subtypes (pan-B, pan-T, T8, T4 and NKH1) and at activation epitopes (IL-2 receptor, TA1 and T11/3) as well, in order to determine the phenotype in association with the activation status of the lymphocytes that are in close contact with hepatocytes; thus, establishing an effector-target cell relationship on the ultrastructural level. We were able to confirm the central role of T8 lymphocytes being the predominant type of lymphocytes in close contact with liver cells in the space of Disse. A certain percentage of these cells expressed "activation" markers as IL-2 receptor, TA1 and T11/3. In acute hepatitis, the NK lymphocytes made up a fifth of all lymphocytes, whereas their number dropped below 10% in the chronic stage. There was a vague correlation between the inflammatory activity of the disease and the expression of HLA antigens (both classes I and II) on inflammatory cells and also on hepatocytes. The results did not show significant differences between hepatitis B and non-A, non-B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunoelectron microscopic observations on the inflammatory infiltrates and HLA antigens in hepatitis B and non-A, non-B. 311 53

Phytohaemagglutinin (PHA)-stimulated peripheral blood lymphocytes were examined sequentially for changes in volume, the appearance of cell membrane receptors and nucleic acid synthesis. The kinetics of appearance of activation antigens were compared with the progress of the cell through the separate events of volume growth and nucleic acid syntheses, to determine points at which regulation of receptors may control further progress through the cell cycle. In all samples tested there was a consistent pattern of response in the proportion of cells progressing through the cell cycle. Most of the T cells increased in size (mean 82% at 24 hr), fewer cells entered the Gla/Glb phase with the onset of RNA synthesis (mean 68% at 48 hr) and even fewer entered DNA synthesis (mean 42% at 72 hr). The time-course of appearance and the number of cells expressing IL-2 receptors were almost identical with that of cells responding by RNA synthesis. A similar correlation was observed between expression of the transferrin receptor and DNA synthesis. Addition of anti-Tac antibody temporarily suppressed the onset of RNA synthesis and antibodies to the transferrin receptor suppressed DNA synthesis. These linkages are further evidence that IL-2 and transferrin are the specific signals for cellular RNA and DNA synthesis. With optimal concentrations of PHA, addition of IL-2 did not increase the proportion of cells bearing activation antigens or undergoing nucleic acid synthesis. Suboptimal concentrations of PHA produced a small reduction in the number of cells expressing the IL-2 receptor, but a much greater reduction in the rate of entry into RNA synthesis. There was a consistent increase in all activation parameters tested with the addition of IL-2, but the proportion of cells expressing the transferrin receptor and entering DNA synthesis was consistently lower than that of cells that expressed the IL-2 receptor or entered RNA synthesis. This suggests that regulation of the IL-2 receptor is not responsible for the reduction in the number of cells that proceed to proliferation. The CD2 antigen (T11(1] showed increasing expression in a step-wise fashion after activation, the increases coinciding with the onset of RNA and DNA syntheses.
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PMID:Changes in activation markers and cell membrane receptors on human peripheral blood T lymphocytes during cell cycle progression after PHA stimulation. 326 9

Staphylococcal Enterotoxin A (SEA) at picogram amounts induces high levels of interleukin 2 (IL-2) and interferon in human mononuclear cells. SEA is a stronger inducer of IL-2 than phytohemagglutinin, leukoagglutinin, and concanavalin A. The IL-2 induction is very rapid with maximal levels being reached after 18 to 24 hr. The IL-2 concentration decreases rapidly and almost no IL-2 activity can be detected in supernatants of cells cultured for 3 days or more. Maximal DNA synthesis is recorded 3 days after maximal IL-2 levels have been reached in the culture medium. The DNA synthesis shows a 24 hr delay as compared to the expression of the IL-2 receptor during the initiation phase. An increase in the level of IL-2 receptor expression is apparent as early as 12 hr after stimulation with SEA and maximal expression is reached 48 to 72 hr after stimulation. The percentage of cells expressing the IL-2 receptor is maximal at 96 hr after onset of culture but the surface concentration of the receptor is lower than at 72 hr. The decline in expression of the IL-2 receptor is accompanied by a decline in mean cell size and in DNA-synthesis. The concentration of the T-cell marker T11 increases in parallel with the growing expression of the IL-2 receptor. It remains increased over a longer period than the IL-2 receptor and is still significantly augmented after 10 days' exposure to SEA.
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PMID:Kinetics of IL-2 and interferon-gamma production, expression of IL-2 receptors, and cell proliferation in human mononuclear cells exposed to staphylococcal enterotoxin A. 393 9

CD30 has been extensively studied as a cell surface marker expressed by Reed-Sternberg cells of Hodgkin's disease and other hematologic malignancies, although little is known about its expression by normal lymphoid cells. We therefore characterized the requirements for the induction of CD30 expression and identified the subsets of T cells that express CD30. CD30 is inducible on approximately 15% of normal PBMC stimulated with any of a variety of nonspecific T cell activators, including PHA, Con A, anti-T11(2) + T11(3), and anti-CD3; ionomycin alone induced lower percentages of CD30+ T cells (3 +/- 2%) compared to other stimuli. Maximal numbers of CD30+ cells were observed at 48 to 72 h of activation and the addition of rIL-2 did not affect these kinetics. However, CD30 expression was enhanced by the addition of exogenous rIL-2 to any of the stimuli tested, although rIL-2 alone did not lead to CD30 expression. The induction of CD30 during anti-CD3 mitogenesis was completely inhibitable by anti-IL-2 antibodies and partially inhibitable by rIL-4, indicating a requirement for both TCR triggering and IL-2 for its expression. Dual immunofluorescence analysis revealed that CD30+ cells were confined to CD3+ T cells that coexpressed higher levels of the p55 IL-2 receptor (CD25) than the CD30- population. Furthermore, CD30 expression was restricted to a subset of cells derived from CD45RO+ T cell precursors. Cell cycle analysis showed that CD30+ expression was not cell cycle dependent. Cross-linking of membrane CD30 induced Ca2+ in TCR+, but not TCR- Jurkat T cells. These results demonstrate that CD30 can serve as a T cell signal-transducing molecule and expressed by a unique subset of activated CD45RO+ T cells.
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PMID:CD30 is a signal-transducing molecule that defines a subset of human activated CD45RO+ T cells. 810 64

A high-affinity IL-2 receptor requires two Janus protein tyrosine kinases (JAKs) for IL-2 signal transduction: JAK1 and JAK3. Since transphosphorylation of the two kinases is presumed to occur after receptor engagement we examined the phosphorylation by recombinant JAK3 of a peptide substrate corresponding to the JAK1 activation loop (KAIETDKEYYTVKD), which has two adjacent tyrosines. Mass spectral analysis of the enzymatically phosphorylated peptide showed that the second tyrosine was phosphorylated at a 30-fold greater rate than the first tyrosine. Moreover, no doubly phosphorylated peptide was detected by this analysis. Kinetic analysis of the reactions of singly phosphorylated JAK1 activation loop peptides showed that phosphorylating the first or second tyrosine decreased the k(cat)/K(m) for the phosphorylation of the other 115- and 26-fold, respectively. Singly changing each side chain of the KEYYTV portion of the peptide to a methyl group (alanine) yielded substrates comparable to the wild-type sequences in all cases except that of the first or second tyrosine, which showed a 153- or 70-fold drop in k(cat)/K(m), respectively. Using libraries of immobilized peptides with all 20 naturally occurring amino acids substituted for Y9 or T11 showed that the JAK3 tolerated substitution at T11 but prefers large hydrophobic amino acids at Y9. These results show that JAK3 does not act processively on the JAK1 activation loop in vitro and illustrate the role of Y9 in the recognition of the preferred site of phosphorylation which is Y10.
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PMID:Mechanism of Janus kinase 3-catalyzed phosphorylation of a Janus kinase 1 activation loop peptide. 1255 72


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