scholarly journals Functional differences between two Fc receptor ITAM signaling motifs

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3302-3307 ◽  
Author(s):  
IE Van den Herik-Oudijk ◽  
MW Ter Bekke ◽  
MJ Tempelman ◽  
PJ Capel ◽  
JG Van de Winkel
Keyword(s):  
Ligand Binding ◽  
Antigen Presentation ◽  
Interleukin 2 ◽  
Fc Receptor ◽  
Gamma Chain ◽  
Alpha Chain ◽  
Receptor Complexes ◽  
Functional Differences ◽  
Cytoplasmic Tails ◽  
Chimeric Molecules

Most Ig receptors exist as multi-subunit complexes with a unique ligand binding alpha chain and a common signaling FcR gamma-chain. The myeloid Fc gamma RIIa (CD32) appears unique among FcR because both ligand- binding and signaling capacity are found in the alpha chain. Within the cytoplasmic tails of Fc gamma RIIa and FcR gamma-chain similar, but not identical, activatory motifs (ITAMs) have been defined, in which tyrosines play an important role. Previously, Fc gamma RIIa-ITAM was shown to be critical for both proximal and distal activatory functions in IIA1.6 B-cell transfectants. Triggering of interleukin-2 (IL-2) release and antigen presentation was absent in Fc gamma RIIa, but not in FcR gamma-chain receptor complexes. We now assessed the capacity of Fc gamma RIIa wild-type and Fc gamma RIIa/gamma chimeric molecules to trigger IL-2 production and antigen presentation by B cells. Both of these functions could solely be triggered by receptors containing the FcRIIa was capable of functional interaction with FcR gamma-chain, thus reconstituting the capacity to trigger IL-2 release and antigen presentation. These data document qualitative differences between Fc receptor ITAMs.

scholarly journals Kinetic analysis of ligand binding to interleukin-2 receptor complexes created on an optical biosensor surface

1996 ◽  
Vol 5 (12) ◽  
pp. 2468-2478 ◽  
Author(s):  
David G. Myszka ◽  
Peter R. Arulanantham ◽  
Theodore Sana ◽  
Zining Wu ◽  
Thomas A. Morton ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Kinetic Analysis ◽  
Interleukin 2 ◽  
Optical Biosensor ◽  
Receptor Complexes ◽  
Interleukin 2 Receptor

scholarly journals Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor alpha, beta, and gamma chains.

1995 ◽  
Vol 129 (1) ◽  
pp. 55-64 ◽  
Author(s):  
A Hémar ◽  
A Subtil ◽  
M Lieb ◽  
E Morelon ◽  
R Hellio ◽  
...  
Keyword(s):  
Intracellular Localization ◽  
Interleukin 2 ◽  
Surface Protein ◽  
Degradation Pathway ◽  
Endocytic Pathway ◽  
Gamma Chain ◽  
Recycling Endosomes ◽  
Alpha Chain ◽  
Late Endosomes ◽  
Alpha Beta

Members of the cytokine receptor family are composed of several noncovalently linked chains with sequence and structure homologies in their extracellular domain. Receptor subfamily members share at least one component: thus the receptors for interleukin (IL) 2 and IL15 have common beta and gamma chains, while those for IL2, 4, 7, and 9 have a common gamma chain. The intracellular pathway followed by IL2 receptors after ligand binding and endocytosis was analyzed by immunofluorescence and confocal microscopy in a human T lymphocytic cell line. Surprisingly, the alpha, beta, and gamma chains had different intracellular localizations after being endocytosed together. The alpha chain was always in transferrin-positive compartments (early/recycling endosomes), both at early and late internalization times, but was never detected in rab7-positive compartments (late endosomes). On the other hand, at late internalization times, the beta and gamma chains were excluded from transferrin-positive organelles and did not colocalize with alpha. Furthermore, beta could be found in rab7-positive vesicles. These differences suggest that the alpha chain recycles to the plasma membrane, while the beta and gamma chains are sorted towards the degradation pathway. The half-lives of these three chains on the cell surface also reflect their different intracellular fates after endocytosis. The beta and gamma chains are very short-lived polypeptides since their half-life on the surface is only approximately 1 h, whereas alpha is a much more stable surface protein. This shows for the first time that components of a multimeric receptor can be sorted separately along the endocytic pathway.

scholarly journals Proteomic characterisations of ulcerative colitis endoscopic biopsies associate with clinically relevant histological measurements of disease severity

2021 ◽  
pp. jclinpath-2021-207718
Author(s):  
Aaron M Gruver ◽  
Matt D Westfall ◽  
Bradley L Ackermann ◽  
Salisha Hill ◽  
Ryan D Morrison ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Accuracy Assessment ◽  
Interleukin 2 ◽  
Proteome Analysis ◽  
Scoring Systems ◽  
Cell Junction ◽  
Interleukin 17 ◽  
Gamma Chain ◽  
Novel Approach ◽  
Interleukin 23

Aims and methodsAccurate protein measurements using formalin-fixed biopsies are needed to improve disease characterisation. This feasibility study used targeted and global mass spectrometry (MS) to interrogate a spectrum of disease severities using 19 ulcerative colitis (UC) biopsies.ResultsTargeted assays for CD8, CD19, CD132 (interleukin-2 receptor subunit gamma/common cytokine receptor gamma chain), FOXP3 (forkhead box P3) and IL17RA (interleukin 17 receptor A) were successful; however, assays for IL17A (interleukin 17A), IL23 (p19) (interleukin 23, alpha subunit p19) and IL23R (interleukin 23 receptor) did not permit target detection. Global proteome analysis (4200 total proteins) was performed to identify pathways associated with UC progression. Positive correlation was observed between histological scores indicating active colitis and neutrophil-related measurements (R2=0.42–0.72); inverse relationships were detected with cell junction targets (R2=0.49–0.71) and β-catenin (R2=0.51–0.55) attributed to crypt disruption. An exploratory accuracy assessment with Geboes Score and Robarts Histopathology Index cut-offs produced sensitivities/specificities of 72.7%/75.0% and 100.0%/81.8%, respectively.ConclusionsPathologist-guided MS assessments provide a complementary approach to histological scoring systems. Additional studies are indicated to verify the utility of this novel approach.

Interleukin-2 receptor alpha-chain (CD25) expression on leukaemic blasts is predictive for outcome and level of residual disease in AML

2009 ◽  
Vol 45 (9) ◽  
pp. 1692-1699 ◽  
Author(s):  
Monique Terwijn ◽  
Nicole Feller ◽  
Anna van Rhenen ◽  
Angèle Kelder ◽  
Guus Westra ◽  
...  
Keyword(s):  
Residual Disease ◽  
Interleukin 2 ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Cd25 Expression ◽  
Interleukin 2 Receptor ◽  
Receptor Alpha Chain
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