Differential peptide binding to CD40 evokes counteractive responses.

Details

Serval ID
serval:BIB_08C2F641969D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Differential peptide binding to CD40 evokes counteractive responses.
Journal
Human Immunology
Author(s)
Khan S., Alonso L., Roduit C., Bandyopadhyay S., Singh S., Saha S., Tacchini-Cottier F., Roy S., Dietler G., Kasas S., Das P., Krishnasastry M.V., Saha B.
ISSN
1879-1166 (Electronic)
ISSN-L
0198-8859
Publication state
Published
Issued date
2012
Volume
73
Number
5
Pages
465-469
Language
english
Abstract
The antigen-presenting cell-expressed CD40 is implied in the regulation of counteractive immune responses such as induction of pro-inflammatory and anti-inflammatory cytokines interleukin (IL)-12 and IL-10, respectively. The mechanism of this duality in CD40 function remains unknown. Here, we investigated whether such duality depends on ligand binding. Based on CD40 binding, we identifed two dodecameric peptides, peptide-7 and peptide-19, from the phage peptide library. Peptide-7 induces IL-10 and increases Leishmania donovani infection in macrophages, whereas peptide-19 induces IL-12 and reduces L. donovani infection. CD40-peptide interaction analyses by surface plasmon resonance and atomic force microscopy suggest that the functional differences are not associated with the studied interaction parameters. The molecular dynamic simulation of the CD40-peptides interaction suggests that these two peptides bind to two different places on CD40. Thus, we suggest for the first time that differential binding of the ligands imparts functional duality to CD40.
Keywords
Amino Acid Sequence, Antigens, CD40/immunology, Antigens, CD40/metabolism, Binding Sites, Cells, Cultured, Humans, Interleukin-10/immunology, Interleukin-10/metabolism, Interleukin-12/immunology, Interleukin-12/metabolism, Leishmania donovani/immunology, Leishmaniasis, Visceral/immunology, Leishmaniasis, Visceral/parasitology, Macrophages/drug effects, Macrophages/immunology, Microscopy, Atomic Force, Molecular Dynamics Simulation, Molecular Sequence Data, Oligopeptides/immunology, Oligopeptides/metabolism, Peptide Library, Protein Binding, Surface Plasmon Resonance
Pubmed
Web of science
Create date
09/06/2012 18:08
Last modification date
20/08/2019 12:31
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