Peptide Mimicry of AICL Inhibits Cytolysis of NK Cells by Blocking NKp80-AICL Recognition

Abstract

AICL has been identified as a ligand of the activating NK cell receptor NKp80, but the interaction sites of NKp80-AICL were unknown. In this study, a 3-D model of AICL was constructed by using online server 3D-JIGSAW. Three highly conserved sequences of AICL on the surface of the AICL 3-D model were synthesized, and named as P1, P2 and P3, respectively. Flow cytometric analysis demonstrated that these peptides were able to compete with anti-NKp80 mAb on NKp80 binding activity in a dose-dependent manner. Moreover, P1 or P2 exerted inhibitory effects on NKp80-AICL mediated cytotoxicity of both fresh PBMCs and purified NK cells in ⁵¹Cr release cytotoxicity assay. These results demonstrated that P1 and P2 sequences on AICL might be considered as the potential sites of NKp80-AICL interaction.

Keywords:

• NK cells
• NKp80
• AICL
• peptides
• binding activity
• cytotoxicity

ACKNOWLEDGMENT

This work was supported by Natural Science Foundation of China (#30801007, #30721002, #30870998, #30630059) and Ministry of Science & Technology of China (973 Basic Science Project #2007CB512807, #2006CB806504, #2010CB911901, #2007CB512405).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.