Differential peptide binding to CD40 evokes counteractive responses

详细信息	查看全文 | 推荐本文 |

• 作者：Srijit Khan^a ; Livan Alonso^b ; Charles Roduit^b ; Syamdas Bandyopadhyay^a ; Shailza Singh^a ; Shipra Saha^a ; Fabienne Tacchini-Cottier^c ; Somenath Roy^d ; Giovanni Dietler^b ; Sandor Kasas^b ; Pradeep Das^e ; M.V. Krishnasastry^a ; Bhaskar Saha^a ; ^{sahab@nccs.res.in}
• 关键词：Leishmania ; Macrophages ; CD40 ; CD40-ligand ; Costimulation
• 刊名：Human Immunology
• 出版年：2012
• 期刊代码：75_01988859
• 类别：bio
• 出版时间：May, 2012
• 卷：73
• 期：5
• 页码：465-469
• 文件大小：1629 K

摘要

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.