KIR killer-cell immunoglobulin—like receptor Fu qiang

Outline  Diseases associated with KIR Diseases associated with KIR  Construction  Function

Several diseases associated with NK cell and KIR  Graves  Behcet's disease  Ankylosing spondylitis

Graves Thyroid Eye Disease

Behcet's disease

Ankylosing spondylitis

Outline  Diseases associated with KIR  Construction Construction  Function

What’s KIR  KIR is the killer-cell immunoglobulin—like receptor which is on the surface of natural killer cell.  It can regulate the activity of the NK cell by recognizing and binding HLA2 allele on the target cell specifically

Construction of KIR gene  KIR gene locates on the 19ql3.42 humane chromosome  Usually KIR gene has 9 extrons 1,2 encode the Leader Peptide 3,4 and 5 encode the extracellular D0,D1 D2 Ig-like domains 6,7encode the sequence between domains and the transmembrane segment 8,9encode the intracellular segment

Variety of KIR gene  1.The number of KIR gene is different in different NK cell clone.  2.There are many different allelomorph in at the same site.

Construction and classification of KIR Different gene Different construction

Construction and classification of KIR KIR is composed of  Extracellular D0,D1,D2 Ig-like domains  transmembrane fragment  intracellular fragment

Classification of KIR Base on the number of Ig—domains in the ext racellular region Based on the length of the cytoplasmic tail KIR2D (p58) KIR3D (p70) L-type have two ITIM S-type have no ITIM

KIR2DL ITIM C -end N -end Binding to DAP-12 KIR can also be divided into inhibitory and activation types

Ligand specificity of KIR KIR on the surface of the NK cell can recognize and bind HLA2 Ⅰ molecule on the target cell specifically

KIR-mediated signal transduction

Outline  Diseases associated with KIR  Construction  Function Function

Function of KIR

KIR’s biological functions  1.Functions in autoimmune disease  2.Functions in pregnancy  3.Functions in hemopoietic stem cell transplantation prognosis

1.Functions in autoimmune disease KIR and it’s ligand are both with high variety  diabetes mellitus  psoriasis( 银屑病 )  scleriasis( 硬皮病 )

2.Functions in pregnancy  NK cell in decidua plays an important role in allorecognizition during the pregnancy.  NK cell regulate the immune response at the joint between the fetus and matrix by the inhibitory or activation receptor selectively bind the expression of the HLA2 Ⅰ allele in the trophoderm.

3.Functions in hemopoietic stem cell transplantation prognosis  When transplantation we should consider the matching of both HLA and KIR.  NK cell may take part in the pathology process of Graft Versus Host Disease (GVHD) after transplantation of homologous bone marrow..

An experiment of KIR  Analyze the KIR gene type of 18 Leukemia patients whose HLA are fine matched including 13 HLA+, KIR- pair;3 HLA+ and KIR+ pair;2 HLA+,KIR- pair but with no affinity, and monitor the reconstruction of the NK receptor. RESULTS: 8 have good reconstruction of the NK receptor 6-9months later including KIR-;5 have a low KIR express 1year after transplantation,3 of them reach to the donor’s KIR level 3 years later;5 have serious complication. (a donor and a recipient makes a pair ; “+” means matches well, “-” means not match)

Epilogue NK cell is a very important component of innate immune system. It’s activity depends on the interaction between the receptors and ligands.KIR is one of the important receptor which bind to HLA2 Ⅰ specifically.Study KIR deeply,we can know the mechanism of NK’s biologic functions on molecule level. The study of the functions in autoimmune disease, pregnancy, hemopoietic stem cell transplantation prognosis will do good to the clinical usage of NK cell.

Team member: Xu gang Wang wentao Zhao bin Li qinghu Guo faling Wan xueshuai 04 临六 3 班之 3406

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