title: Differential peptide binding to CD40 evokes counteractive responses.
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.
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune, India.
authors.forename: Srijit
authors.initials: S
authors.lastname: Khan
authors.forename: Livan
authors.initials: L
authors.lastname: Alonso-Sarduy
authors.forename: Livan
authors.initials: L
authors.lastname: Alonso
authors.forename: Charles
authors.initials: C
authors.lastname: Roduit
authors.forename: Syamdas
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Shailza
authors.initials: S
authors.lastname: Singh
authors.forename: Shipra
authors.initials: S
authors.lastname: Saha
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dietler
authors.forename: Sandor
authors.initials: S
authors.lastname: Kasas
authors.forename: Pradeep
authors.initials: P
authors.lastname: Das
authors.forename: M V
authors.initials: MV
authors.lastname: Krishnasastry
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D007893:Leishmania donovani / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D019151:Peptide Library; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D019013:CD40 Antigens; C508609:IL10 protein, human; D009842:Oligopeptides; D019151:Peptide Library; D016753:Interleukin-10; D018664:Interleukin-12