scholarly journals A generic cell surface ligand system for studying cell-cell recognition

2019 ◽  
Author(s):  
Eleanor M Denham ◽  
Michael I Barton ◽  
Susannah M Black ◽  
Marcus J Bridge ◽  
Ben de Wet ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Density ◽  
Cell Receptor ◽  
Surface Receptors ◽  
Ligand System ◽  
Ligand Interactions ◽  
A Cell ◽  
Surface Ligand ◽  
Receptor Biology ◽  
Cell Cell

AbstractDose-response experiments are a mainstay of receptor biology studies and can reveal valuable insights into receptor function. Such studies of receptors that bind cell surface ligands are currently limited by the difficulty in manipulating the surface density of ligands at a cell-cell interface. Here we describe a generic cell surface ligand system that allows precise manipulation of cell surface ligand densities over several orders of magnitude. We validate the system for a range of immunoreceptors, including the T cell receptor (TCR), and show that this generic ligand stimulates via the TCR at a similar surface density as its native ligand. This system allows the effect of surface density, valency, dimensions, and affinity of the ligand to be manipulated. It can be readily extended to other receptor-cell surface ligand interactions, and will facilitate investigation into the activation of, and signal integration between, cell surface receptors.

scholarly journals A generic cell surface ligand system for studying cell–cell recognition

PLoS Biology ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. e3000549 ◽  
Author(s):  
Eleanor M. Denham ◽  
Michael I. Barton ◽  
Susannah M. Black ◽  
Marcus J. Bridge ◽  
Ben de Wet ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Recognition ◽  
Ligand System ◽  
Surface Ligand ◽  
Cell Cell

Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3112-3120 ◽  
Author(s):  
Shu Shun Li ◽  
Zhiwen Liu ◽  
Mehmet Uzunel ◽  
Karl-Gösta Sundqvist
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
Surface Expression ◽  
Lymphocyte Adhesion ◽  
Surface Receptors ◽  
Terminal Domain ◽  
Thrombospondin 1 ◽  
A Cell ◽  
Surface Ligand ◽  
Quiescent T Cells

Abstract Lymphocyte adhesion to cells and extracellular matrix (ECM) via integrins plays a pivotal role for the function of the immune system. We show here that endogenous thrombospondin-1 (TSP-1) is a cell-surface ligand for cis interaction of surface receptors in T lymphocytes controlled by integrins and the T-cell antigen receptor (TCR/CD3). Stimulation of CD3 triggers rapid surface expression of TSP-1 in quiescent T cells, whereas activated cells express TSP-1 constitutively. Endogenous TSP-1 is attached to lipoprotein receptor-related protein 1 (LRP1/CD91) and calreticulin (CRT) on the cell surface through its NH2-terminal domain. Adhesion via integrins to ICAM-1 or ECM components up-regulates TSP turnover dramatically from a low level in nonadherent cells, whereas CD3 stimulation inhibits TSP turnover through interference with CD91/CRT-mediated internalization. Integrin-associated protein (IAP/CD47) is essential for TSP turnover and adhesion through interaction with the C-terminal domain of TSP-1 in response to triggering signals delivered at the NH2-terminal. These results indicate that endogenous TSP-1 connects separate cell-surface receptors functionally and regulates T-cell adhesion.

scholarly journals Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes.

1981 ◽  
Vol 153 (6) ◽  
pp. 1615-1628 ◽  
Author(s):  
D T Fearon ◽  
I Kaneko ◽  
G G Thomson
Keyword(s):  
Cell Surface ◽  
Polymorphonuclear Leukocytes ◽  
Plasma Membranes ◽  
Antibody Fragment ◽  
Cell Receptor ◽  
Molar Ratio ◽  
Surface Receptors ◽  
C3b Receptor ◽  
Tetramethylrhodamine Isothiocyanate ◽  
Human Polymorphonuclear Leukocytes

C3b receptors on human polymorphonuclear leukocytes (PMN) were nonrandomly distributed in small clusters on the plasma membranes of these cells when assessed by indirect immunofluorescence at 0 degree C using monospecific rabbit Fab' or F(ab')2 anti-C3b receptor and tetramethylrhodamine isothiocyanate (TRITC)-conjugated goat IgG anti-F(ab')2. When PMN were incubated with the bivalent anti-C3b receptor at 37 rather than at 0 degree C, almost no immunofluorescence was observed, which indicates that the C3b receptor-F(ab')2 complexes had been rendered inaccessible to TRITC-IgG anti-F(ab')2. Endocytosis of the anti-C3b receptor ligand was quantitated by measuring the binding 131I-IgG anti-F(ab')2 by PMN that had previously taken up 125I-F(ab')2 anti-C3b receptor at 0 and at 37 degree C, respectively. There was a constant 2: 1 molar ratio of anti-F(ab')2 to anti-C3b receptor with PMN that had been incubated with the first antibody at 0 degree C. In contrast, when increments of F(ab')2 anti-C3b receptor were taken up by the cells at 37 degree C, there was a dose-related decline in this molar ratio to a minimum of 0.2 molecules of anti-F(ab')2 anti-F(ab')2 bound per molecule of PMN-associated anti-C3b receptor. 125I-F(ab')2 anti-C3b receptor taken up by PMN at 37 degree C was also inaccessible to release by proteolytic treatment of the cells with pronase. The rate of endocytosis of 125I-F(ab')2 anti-C3b receptor was rapid as the PMN-bound antibody fragment became inaccessible to 131I-IgG anti-F(ab')2 within 10 min during incubation of the cells at 37 degree C. In contrast to these findings, 125I-Fab' anti-C3b receptor that was taken up by PMN at 37 degree C remained accessible to both 131I-IgG anti-F(ab')2 and to proteolytic release by pronase, which suggests that monovalent interaction of ligand with C3b receptors was not sufficient for induction of endocytosis. The requirement for multivalency was also demonstrated using the C3b-OR, the normal ligand for the C3b receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell receptor. 125I-C3b-OR was specifically bound by PMN but remained on the cell surface, as determined by its accessibility to pronase, unless it was cross-linked with F(ab')2 anti-C3. Although C3b receptors on PMN do not mediate internalization of adsorptive pinocytosis of soluble ligand indicates their potential for the clearance of C3b-bearing immune complexes without recruitment of other cell surface receptors.

scholarly journals Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies

2010 ◽  
Vol 38 (5) ◽  
pp. 1349-1355 ◽  
Author(s):  
Thomas A. Bowden ◽  
Max Crispin ◽  
E. Yvonne Jones ◽  
David I. Stuart
Keyword(s):  
Cell Surface ◽  
Viral Entry ◽  
Cell Attachment ◽  
Structural Information ◽  
Cell Receptor ◽  
Specific Protein ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Entry Inhibitors ◽  
Animal Pathogens

Members within the paramyxovirus subfamily Paramyxovirinae constitute a large number of highly virulent human and animal pathogens. The glycoproteins present on these viruses are responsible for mediating host cell attachment and fusion and are key targets for the design of antiviral entry inhibitors. In the present review, we discuss recent structural studies which have led to a better understanding of the various mechanisms by which different paramyxoviruses use their attachment glycoproteins to hijack specific protein and glycan cell-surface receptors to facilitate viral entry. It is observed that the paramyxovirus attachment glycoprotein consists of a conserved overall structure which includes an N-terminal six-bladed β-propeller domain which is responsible for cell receptor binding. Crystal structures of this domain from different biomedically important paramyxoviruses, including measles, Nipah, Hendra, Newcastle disease and parainfluenza viruses, alone and in complex with their functional cell-surface receptors, demonstrate three contrasting mechanisms of receptor engagement that paramyxoviruses have evolved to confer discreet protein- and glycan-receptor specificity. This structural information highlights the adaptability of the paramyxovirus attachment glycoprotein surface and the potential for the emergence of new and potentially harmful viruses in human hosts.

Gingipains Inactivate a Cell Surface Ligand onPorphyromonas gingivalisThat Induces TLR2- and TLR4-Independent Signaling

2006 ◽  
Vol 50 (4) ◽  
pp. 315-325 ◽  
Author(s):  
Mami Kishimoto ◽  
Atsutoshi Yoshimura ◽  
Mariko Naito ◽  
Kuniaki Okamoto ◽  
Kenji Yamamoto ◽  
...  
Keyword(s):  
Cell Surface ◽  
A Cell ◽  
Surface Ligand

The putative sponge aggregation receptor. Isolation and characterization of a molecule composed of scavenger receptor cysteine-rich domains and short consensus repeats

1998 ◽  
Vol 111 (17) ◽  
pp. 2635-2644 ◽  
Author(s):  
B. Blumbach ◽  
Z. Pancer ◽  
B. Diehl-Seifert ◽  
R. Steffen ◽  
J. Munkner ◽  
...  
Keyword(s):  
Cell Surface ◽  
Scavenger Receptor ◽  
Cell Surface Receptor ◽  
Functional Assay ◽  
Cdna Clones ◽  
The Third ◽  
Short Consensus Repeats ◽  
Isolation And Characterization ◽  
A Cell ◽  
Cell Cell

Porifera (sponges) are the oldest extant metazoan phylum. Dissociated sponge cells serve as a classic system to study processes of cell reaggregation. The reaggregation of dissociated cells is mediated by an extracellularly localized aggregation factor (AF), based on heterophilic interactions of the third order; the AF bridges two cells by ligating a cell-surface-bound aggregation receptor (AR). In the present study we report cloning, expression and immunohistochemical localization of a polypeptide from the marine sponge Geodia cydonium, which very likely represents the AR. The presumed AR gene gives rise to at least three forms of alternatively spliced transcripts of 6.5, 4.9 and 3.9 kb, as detected by northern blotting. Two cDNA clones corresponding to the shorter forms were already reported earlier; here we present an analysis of the largest. All three putative polypeptides feature scavenger receptor cysteine-rich (SRCR) domains. The largest form, SRCR-SCR-Car, is a cell-surface receptor of molecular mass 220 kDa, which is assumed to be the cell-adhesion receptor AR; the second form, SRCR-Re, is also a putative receptor of 166 kDa, while the third form, SRCR-Mo, is a soluble molecule of 129 kDa. The SRCR-SCR-Car molecule consists of fourteen SRCR domains, six short consensus repeats (SCRs), a C-terminal transmembrane domain and a cytoplasmic tail; its fourteenth SRCR domain features an Arg-Gly-Asp tripeptide. To obtain monoclonal antibodies, a 170-amino-acid-long polypeptide that is found in all three forms of the SRCR-containing proteins was expressed in E. coli. In a western blot of sponge cells lysate the monoclonal antibody raised against the recombinant polypeptide recognized two major immuno-reacting polypeptides (220 and 117 kDa) and two minor bands (36 and 32 kDa). The antibody was found to react with antigen(s) predominantly localized on the plasma membranes of cells, especially those of spherulous cells. In a functional assay Fab' fragments of the antibodies suppressed AF-mediated cell-cell reaggregation. Additionally, a recombinant SRCR-soluble fragment effectively inhibited AF-mediated cell-cell reaggregation. We conclude that the 220 kDa SRCR-containing protein of the sponge G. cydonium is very likely the AR.

scholarly journals Human Cancer Antigen Globo H Is a Cell-Surface Ligand for Human Ribonuclease 1

2015 ◽  
Vol 1 (4) ◽  
pp. 181-190 ◽  
Author(s):  
Chelcie H. Eller ◽  
Tzu-Yuan Chao ◽  
Kiran K. Singarapu ◽  
Ouathek Ouerfelli ◽  
Guangbin Yang ◽  
...  
Keyword(s):  
Cell Surface ◽  
Human Cancer ◽  
Cancer Antigen ◽  
A Cell ◽  
Surface Ligand

scholarly journals Receptor-mediated cell mechanosensing

2017 ◽  
Vol 28 (23) ◽  
pp. 3134-3155 ◽  
Author(s):  
Yunfeng Chen ◽  
Lining Ju ◽  
Muaz Rushdi ◽  
Chenghao Ge ◽  
Cheng Zhu
Keyword(s):  
Cell Receptor ◽  
Platelet Glycoprotein ◽  
Surface Receptors ◽  
Binding Interface ◽  
Substrate Rigidity ◽  
Step Model ◽  
Multistep Process ◽  
A Cell ◽  
Biochemical Signals ◽  
Cell Mechanosensing

Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the changing environment. Examples of responses and adaptation include (de)activation, proliferation/apoptosis, and (de)differentiation. Receptor-mediated cell mechanosensing is a multistep process that is initiated by binding of cell surface receptors to their ligands on the extracellular matrix or the surface of adjacent cells. Mechanical cues are presented by the ligand and received by the receptor at the binding interface; but their transmission over space and time and their conversion into biochemical signals may involve other domains and additional molecules. In this review, a four-step model is described for the receptor-mediated cell mechanosensing process. Platelet glycoprotein Ib, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process.

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