Peptide mimicry of AICL inhibits cytolysis of NK cells by blocking NKp80-AICL recognition.
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 (51)Cr release cytotoxicity assay. These results demonstrated that P1 and P2 sequences on AICL might be considered as the potential sites of NKp80-AICL interaction.
Huang
Haihua
H
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Zheng
Xiaodong
X
Tian
Zhigang
Z
Sun
Rui
R
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D018716:Molecular Mimicry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D017433:Protein Structure, Secondary; D055607:Receptors, Natural Killer Cell / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C104778:CLEC2B protein, human; C431711:KLRF1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D055607:Receptors, Natural Killer Cell