Galectin-8 tandem-repeat structure is essential for T-cell proliferation but not for co-stimulation

2011 ◽  
Vol 434 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Valentina Cattaneo ◽  
María V. Tribulatti ◽  
Oscar Campetella
Keyword(s):  
T Cells ◽  
Tandem Repeat ◽  
Cd4 T Cells ◽  
Carbohydrate Recognition ◽  
Inhibition Of Proliferation ◽  
Proliferative Effect ◽  
Linker Peptide ◽  
Repeat Structure ◽  
Carbohydrate Recognition Domains ◽  
Group B

Gal (galectin)-8 is a tandem-repeat Gal containing N-CRDs (Nterminal carbohydrate-recognition domains) and C-CRDs (C-terminal carbohydrate-recognition domains) with differential glycan-binding specificity fused by a linker peptide. Gal-8 has two distinct effects on CD4 T-cells: at high concentrations it induces antigen-independent proliferation, whereas at low concentrations it co-stimulates antigen-specific responses. Associated Gal-8 structural requirements were dissected in the present study. Recombinant homodimers N–N (two N-terminal CRD chimaera) and C–C (two C-terminal CRD chimaera), but not single C-CRDs or N-CRDs, induced proliferation; however, single domains induced co-stimulation. These results indicate that the tandem-repeat structure was essential only for the proliferative effect, suggesting the involvement of lattice formation, whereas co-stimulation could be mediated by agonistic interactions. In both cases, C–C chimaeras displayed higher activity than Gal-8, indicating that the C-CRD was mainly involved, as was further supported by the strong inhibition of proliferation and co-stimulation in the presence of blood group B antigen, specifically recognized by this domain. Classic Gal inhibitors (lactose and thiodigalactoside) prevented proliferation but not co-stimulatory activity, which was inhibited by 3-O-β-D-galactopyranosyl-D-arabinose. Interestingly, Gal-8 induced proliferation of naïve human CD4 T-cells, varying from non- to high-responder individuals, whereas it promoted cell death of phytohaemagglutinin or CD3/CD28 pre-activated cells. The findings of the present study delineate the differential molecular requirements for Gal-8 activities on T-cells, and suggest a dual activity relying on activation state.

Full-length galectin-8 and separate carbohydrate recognition domains: the whole is greater than the sum of its parts?

2020 ◽  
Vol 48 (3) ◽  
pp. 1255-1268
Author(s):  
Alejandro J. Cagnoni ◽  
María F. Troncoso ◽  
Gabriel A. Rabinovich ◽  
Karina V. Mariño ◽  
María T. Elola
Keyword(s):  
Tandem Repeat ◽  
Cell Function ◽  
Full Length ◽  
Carbohydrate Recognition ◽  
Linker Peptide ◽  
Carbohydrate Recognition Domains ◽  
Function Relationship ◽  
Relationship Of ◽  
Group Structures

Galectin-8 (Gal-8) is a tandem-repeat type galectin with affinity for β-galactosides, bearing two carbohydrate recognition domains (CRD) connected by a linker peptide. The N- and C-terminal domains (Gal-8N and Gal-8C) share 35% homology, and their glycan ligand specificity is notably dissimilar: while Gal-8N shows strong affinity for α(2-3)-sialylated oligosaccharides, Gal-8C has higher affinity for non-sialylated oligosaccharides, including poly-N-acetyllactosamine and/ or A and B blood group structures. Particularly relevant for understanding the biological role of this lectin, full-length Gal-8 can bind cell surface glycoconjugates with broader affinity than the isolated Gal-8N and Gal-8C domains, a trait also described for other tandem-repeat galectins. Herein, we aim to discuss the potential use of separate CRDs in modelling tandem-repeat galectin-8 and its biological functions. For this purpose, we will cover several aspects of the structure–function relationship of this protein including crystallographic structures, glycan specificity, cell function and biological roles, with the ultimate goal of understanding the potential role of each CRD in predicting full-length Gal-8 involvement in relevant biological processes.

scholarly journals The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3828-3835 ◽  
Author(s):  
Nicoletta Sorvillo ◽  
Wouter Pos ◽  
Linda M. van den Berg ◽  
Rob Fijnheer ◽  
Luisa Martinez-Pomares ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Mannose Receptor ◽  
Immune Recognition ◽  
Binding Studies ◽  
Macrophage Mannose Receptor ◽  
Carbohydrate Recognition Domains

Abstract ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation by cleaving ultra-large VWF multimers on the surfaces of endothelial cells. Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers, initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura. The formation of autoantibodies depends on the activation of CD4+ T cells. This process requires immune recognition, endocytosis, and subsequent processing of ADAMTS13 into peptides that are presented on MHC class II molecules to CD4+ T cells by dendritic cells (DCs). In the present study, we investigated endocytosis of recombinant ADAMTS13 by immature monocyte-derived DCs using flow cytometry and confocal microscopy. After incubation of fluorescently labeled ADAMTS13 with DCs, significant uptake of ADAMTS13 was observed. Endocytosis of ADAMTS13 was completely blocked by the addition of EGTA and mannan. ADAMTS13 endocytosis was decreased in the presence of a blocking mAb directed toward the macrophage mannose receptor (MR). Furthermore, siRNA silencing of MR reduced the uptake of ADAMTS13 by DCs. In addition, in vitro binding studies confirmed the interaction of ADAMTS13 with the carbohydrate recognition domains of MR. The results of the present study indicate that sugar moieties on ADAMTS13 interact with MR, thereby promoting its endocytosis by APCs.

IL-7 sustains CD31 expression in human naive CD4+ T cells and preferentially expands the CD31+ subset in a PI3K-dependent manner

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2999-3007 ◽  
Author(s):  
Rita I. Azevedo ◽  
Maria Vieira D. Soares ◽  
João T. Barata ◽  
Rita Tendeiro ◽  
Ana Serra-Caetano ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Subsets ◽  
Dependent Manner ◽  
Proliferative Effect ◽  
Interleukin 7 ◽  
Phosphoinositide 3 Kinase ◽  
Homeostatic Cytokines ◽  
Cd31 Expression

Abstract The CD31+ subset of human naive CD4+ T cells is thought to contain the population of cells that have recently emigrated from the thymus, while their CD31− counterparts have been proposed to originate from CD31+ cells after homeostatic cell division. Naive T-cell maintenance is known to involve homeostatic cytokines such as interleukin-7 (IL-7). It remains to be investigated what role this cytokine has in the homeostasis of naive CD4+ T-cell subsets defined by CD31 expression. We provide evidence that IL-7 exerts a preferential proliferative effect on CD31+ naive CD4+ T cells from adult peripheral blood compared with the CD31− subset. IL-7–driven proliferation did not result in loss of CD31 expression, suggesting that CD31+ naive CD4+ T cells can undergo cytokine-driven homeostatic proliferation while preserving CD31. Furthermore, IL-7 sustained or increased CD31 expression even in nonproliferating cells. Both proliferation and CD31 maintenance were dependent on the activation of phosphoinositide 3-kinase (PI3K) signaling. Taken together, our data suggest that during adulthood CD31+ naive CD4+ T cells are maintained by IL-7 and that IL-7–based therapies may exert a preferential effect on this population.

scholarly journals Protection against MUC1 expressing mouse tumours by intra-muscular injection of MUC1 cDNA requires functional CD8+ and CD4+ T cells but does not require the MUC1 tandem repeat domain

2004 ◽  
Vol 109 (5) ◽  
pp. 691-697 ◽  
Author(s):  
Tim Plunkett ◽  
Rosalind Graham ◽  
Isobel Correa ◽  
Robert Sewell ◽  
David Miles ◽  
...  
Keyword(s):  
T Cells ◽  
Tandem Repeat ◽  
Cd4 T Cells ◽  
Repeat Domain

Genomic analysis of C-type lectins

2002 ◽  
Vol 69 ◽  
pp. 59-72 ◽  
Author(s):  
Kurt Drickamer ◽  
Andrew J. Fadden
Keyword(s):  
Biological Effects ◽  
Cell Signalling ◽  
Genomic Analysis ◽  
Binding Activity ◽  
Immunoglobulin Superfamily ◽  
Carbohydrate Binding ◽  
Carbohydrate Recognition ◽  
Calcium Dependent ◽  
Binding Domains ◽  
Carbohydrate Recognition Domains

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell–cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

Activated CD4+ T cells enriched from spleen or colon induce apoptosis in intestinal epithellal cells via fas/fas ligand interactions

2001 ◽  
Vol 120 (5) ◽  
pp. A192-A192
Author(s):  
H TAKAISHI ◽  
T DENNING ◽  
K ITO ◽  
R MIFFLIN ◽  
P ERNST
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Fas Ligand ◽  
Ligand Interactions
Sign in / Sign up

Export Citation Format

Share Document