Characterization of the human interleukin-2 receptor gamma chain gene

Noguchi, Masayuki; Adelstein, Stephen; Cao, Xiqing; Leonard, Warren J.

doi:10.1016/s0021-9258(19)38691-0

Cited by 78 publications

(5 citation statements)

References 29 publications

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“…This result confirms and extends our previous data showing that purified resting CD4 T lymphocytes also express IL-2R␥ only inside the cell. 30 The intracellular expressions we show here are consistent with the fact that IL-2R␥ gene promoter has the characteristics of a constitutively active promoter 43 and that IL-2R␥ mRNA is constitutively expressed in PBL 15 and in monocytes. 44 For human monocytes, IL-2R␥ has been shown to migrate as several Western blot bands, in addition to the classical 64-kD band, 15 which correspond to different levels of N-linked glycosylation.…”

Section: Discussionsupporting

confidence: 86%

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets

David

Bani

Moreau

et al. 1998

Blood

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We have investigated the expression of the three components of the interleukin-2 receptor (IL-2Rα, IL-2Rβ, and IL-2Rγ) on the surface of the various peripheral blood mononuclear cell (PBMC) subsets by flow cytometry analysis. The PBMC were immediately isolated (ficoll) from blood collected on heparin as anticoagulant. The three IL-2R components are absent or only marginally detectable on CD4 T lymphocytes. No expression of the IL-2R chains is found for the B lymphocytes. In most donors, the three chains are not detectable on CD8 T lymphocytes, but for a few of them, IL-2Rβ or IL-2Rγ are clearly expressed. CD56 high (IL-2Rα+) and CD56 low (IL-2Rα−) natural killer (NK) cells express IL-2Rβ, but not IL-2Rγ. IL-2Rγ is expressed by monocytes of all donors although with variable intensity. When blood is collected on other anticoagulants or when cells are isolated 1 day after collection, IL-2Rα, IL-2Rβ, and IL-2Rγ are largely expressed on the surface of most PBMC. This observation provides a possible explanation for divergent data previously reported on IL-2R expression. Finally, we show that IL-2Rγ, which is not detectable on the cell surface of lymphocytes, is nevertheless expressed and stored as an intracellular component. This result is in agreement with the constitutive expression of the IL-2Rγ gene and suggests a specific regulatory mechanism for IL-2Rγ membrane translocation.

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Section: Discussionsupporting

confidence: 86%

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets

David

Bani

Moreau

et al. 1998

Blood

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“…However, in contrast to other IL-2R components, 3/chain mRNA appears to be constitutively expressed in all lymphoid cells. This finding is consistent with the demonstration that the IL-2R 7 promoter sequence is GC-rich and lacks TATA motifs, and suggests that surface expression of 3' chain is likely to be regulated primarily by posttranscriptional mechanisms (15,23). However, lack of suitable reagents has previously prevented detailed examination of cell surface expression of IL-2R 7.…”

supporting

confidence: 83%

“…An expression vector containing IL-2R7 cDNA (pMT2.UCHL1 +.IL-2RT.CD45) was derived from pMT2.LCA.1 (CD45 O-isoform) (24,25), and synthetic oligonucleotides (5'-GCTTCCAAGGATCCGGAAG-3' and 5'-CGCTTCCGGATCCTTGGAAGC-3') by ligating appropriate restriction fragments in frame. The resulting hybrid protein, UCHL1 +.IL-2RT.CD45, contains portions of several proteins in the following order: (a) CD45 leader sequence; (b) CD45 amino acids 1-8 and 202-218; (c) Ib2R 7 amino acids (L1-N232); (d) seven amino acids (RFQGSGS) arising from the synthetic oligonudeotides; and (e) CD45 amino acids 214-1281 (numbering of CD45 and IL-2R7 amino acid residues according to Streuli et al [26] and Noguchi et al [23], respectively).…”

Section: Methodsmentioning

confidence: 99%

Interleukin 2 receptor gamma chain expression on resting and activated lymphoid cells.

Nakarai

Robertson

Streuli

et al. 1994

The Journal of Experimental Medicine

122

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SummaryThe interleukin 2 receptor (IL-2K) is known to be comprised of at least three genetically distinct subunits termed c~, B, and 3/. These chains can be expressed individually or in various combinations resulting in distinct receptors with different affinities for IL-2. In contrast to a and/8, the cell surface expression of the 3' chain protein previously has not been well-characterized. To examine cell surface expresssion of IL-2R3, on hematopoietic cells, we developed two new monoclonal antibodies (mAbs) specific for this protein. Both 1All (immunoglobulin [IgG1]) and 3Gll (IgM) specifically reacted with murine cells transfected with IL-2K3" cDNA, and immunoprecipitation studies indicated that both antibodies precipitated a protein of approximately 62-65 kD. Scatchard analysis of IL-2 binding to murine cells transfected with cDNA-encoding combinations of IL-2R components demonstrated that neither B nor 3, chain bind IL-2 with measurable affinity, but coexpression of both/8 and 3' is sufficient to form an intermediate affinity receptor. In the absence of 3' chain,/8 chain interacts with ot chain to form a "pseudo-high" affinity receptor. In contrast, 3' chain does not appear capable of interacting with a chain in the absence of/8 chain. Thus, 3' chain appears to interact only with/~, but ~ chain is capable of interacting with both ot and 3'. Using the newly developed mAbs to examine cell surface expression by immunofluorescence, resting T cells were found to express low levels of 3' chain without detectable a or/8. Early after mitogen stimulation, T cells expressed higher levels of oe,/~, and 3'. However, at later time points, T cells expressed ot and 3' in marked excess over/8. Thus, formation of high affinity IL-2R on activated T cells was primarily limited by/8 chain expression. In contrast, resting natural killer (NK) cells constitutively expressed IL-2RB without detectable cr or 3'. After activation with either IL-2 or IL-12, expression of both c~ and 3' transiently increased and then returned to very low levels. Expression of functional IL-2R on resting and activated NK cells, therefore, appeared to be primarily limited by the expression of 3' chain. IL-2 binding studies with resting NK cells confirmed the results ofimmunofluorescence studies indicating the presence of very low numbers of intermediate affinity (/~3') receptors for IL-2 on these cells. NK cells obtained from patients receiving IL-2 therapy were phenotypically similar to resting NK cells. These studies have identified marked differences in IL-2R composition in two different types of cytotoxic lymphocytes, further underscoring the complexity of this receptor/ligand system. With new reagents specific for IL-2R3", it will now be possible to examine further the functional significance of these differences.

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“…The transcript is 3218 bp and creates a 272 aa protein. It contains 8 exons, from which 6 are coding, while exon 8 and the 5 fragment from exon 1 are noncoding [124]. A pivotal enhancer element (positive regulatory region-PRRI) in the promoter region is located from −299 to −228 relevant to the TSS and binds NF-κB [125].…”

Section: Il2ra Gene Structurementioning

confidence: 99%

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Piotrowska

Gliwiński

Trzonkowski

et al. 2021

IJMS

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Regulatory T cells (Tregs) exert a highly suppressive function in the immune system. Disturbances in their function predispose an individual to autoimmune dysregulation, with a predominance of the pro-inflammatory environment. Besides Foxp3, which is a master regulator of these cells, other genes (e.g., Il2ra, Ctla4, Tnfrsf18, Ikzf2, and Ikzf4) are also involved in Tregs development and function. Multidimensional Tregs suppression is determined by factors that are believed to be crucial in the action of Tregs-related genes. Among them, epigenetic changes, such as DNA methylation, tend to be widely studied over the past few years. DNA methylation acts as a repressive mark, leading to diminished gene expression. Given the role of increased CpG methylation upon Tregs imprinting and functional stability, alterations in the methylation pattern can cause an imbalance in the immune response. Due to the fact that epigenetic changes can be reversible, so-called epigenetic modifiers are broadly used in order to improve Tregs performance. In this review, we place emphasis on the role of DNA methylation of the genes that are key regulators of Tregs function. We also discuss disease settings that have an impact on the methylation status of Tregs and systematize the usefulness of epigenetic drugs as factors able to influence Tregs functions.

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Characterization of the human interleukin-2 receptor gamma chain gene

Cited by 78 publications

References 29 publications

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets

Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets

Interleukin 2 receptor gamma chain expression on resting and activated lymphoid cells.

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

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