The inhibitory effects of synthetic short peptides, mimicking MICA and targeting at NKG2D receptors, on function of NK cells.
NKG2D is an activating receptor expressed on most of human NK cells, one of whose ligands is MICA. Based on the crystal structure of NKG2D-MICA complex, we synthesized three short peptides (P1, P2 and P3), mimicking functional alpha1 and alpha2 domain of MICA. The inhibitory effects of three peptides on NK-92 cells, a human NK cell line against Hela cells were observed and the inhibitory percentage was 38% at maximum for P1+P2+P3 in concentration of 1nM. The same peptides had no effect on NK-92 cell against target cells lacking MICA (K562 cells line). The unrelated peptides as controls had no effect on the system. Two peptides (P2 and P3) were prolonged at one or both ends, and the longer forms of peptides exerted stronger inhibitory effects than their shorter forms. Each combination of two peptides exerted a stronger function than single peptide (P1, P2, P3), indicating that shedding of longer amino acid sequence of alpha1 domain or more domain sites of MICA are better than shorter sequence and fewer sites. P1+P2+P3 revealed the almost same inhibitory rate as the soluble MICA (sMICA). P1+P2+P3 were also able to alleviate the concanavalin A-induced murine autoimmune hepatitis in vivo, conforming the similarity of NKG2D between human and mice. The results demonstrate that MICA-mimicking peptides will be useful to search the specific functional sites for NKG2D-MICA interaction, but also promising in explaining NKG2D-related autoimmunity.
Zhang
Bin
B
School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, China.
Wei
Haiming
H
Zheng
Xiaodong
X
Zhang
Jian
J
Sun
Rui
R
Tian
Zhigang
Z
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D002460:Cell Line; D002857:Chromium / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D019693:Hepatitis, Autoimmune / Q000188:drug therapy; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D055607:Receptors, Natural Killer Cell; D013045:Species Specificity
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010455:Peptides; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D002857:Chromium; D003208:Concanavalin A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase