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The Molecular Basis Of Killer Cell Inhibitory Receptor P58 And Their Ligand HLA-C In Han Nationality Of GuangDong

Posted on:2003-12-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:X H PanFull Text:PDF
GTID:1104360092965531Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
There is no technical problems for hematopoietic stem cell transplant (HSCT), but badly short of HLA matched donors is the hindrance. It is difficult to get succeed in HLA mismatched HSCT because graft- verse- host- disease(GVHD), the unconquer holdback of clinical HSCT. Researches on immunity inhibitory receptors break a new path for HSCT without GVHD, the dream of HSCT physician and patients. Killer cells including natural killer cells( NK) and cytotoxic T lymphocyte (CTL) are important effective cells in GVHD development. Killer cell inhibitory receptors(KIR) expressed on NK and T cells are the key moleculars in immunity cytotoxicity regulation. P58, including P58.1 and P58.2, is a member of KIR superfamily and can be divided into 2DLK 2DL2 - 2DL3 and 2DL4 according to their structure characteristics. The specific ligands of P58 are human leukocyte antigen C (HLA-C) expressed in target cells. P58 conduct negative signals and inhibit NK and CTL activation depending on junction with HLA-C in target cells. There is strict ligand specific between P58 and HLA-C, so P58 can effectively coupling HLA-C of self cells, but cannot binding HLA-C mutated in structure and quantity, such as tumor cells or affection cells, allogenitic cells, and have the ability to kill them.There are some reports about the structure , function and GVHD relevant of P58, but few reports about P58 in Chinese. Based on the important rules of P58 in immunity regulation and the possible using in GVHD prevention. The makeup of P58 and itsGVHD relation in the Han nationality of Contonese (HNC) have been studied.K Distribution of P58> HLA-C gene frequence: The results of HLA-C gene typing shown the mainly distributed HLA-C genes in the HNC are P58.2 binding gene, HLA-Cwl , 3 , 7 which gene frequences are 0.29, 0.27, 0.38 respectively. Gene frequences of HLA-Cw2, -Cw4, -Cw6 binding P58.1 are lower than 0.05. HLA-Cw6, -Cw9, -Cwl0 haven't been identified in this study.2DL1-4, the member of P58 gene family, were identified in the HNC. Among of them, 2DL4 gene frequence was detected almost in 99% studied objects and the gene frequence was 0.86. The secondly gene frequence was 2DL1 and the lowest gene frequence of P58 was 2DL2 . P58 gene frequence were 2DL4( 0.86)>2DL1(0.69)> 2DL3(0.56)>2DL2(0.41). The result indicates a distribution of HLA-C gene frequency in the HNC were mainly P58.2 binding type, that were HLA-Cw1, 3, 7 and different from other reported groups, especially those Western populations.2, Distribution of P58+ cells in immunity subset: P58 gene are mainly expressed in NK, CD3+, CD4+and CD8+ cells. The ratios of P58+ cells in NK cells were higher than that of CD3+cells and the ratios of P58+ cells in CD8+ cells higher than that of CD4+. The ratios variety pattern of P58.1+ and P58.2+ cell in immunity subsets are consistent, but the ratios of P58.2* cells higher than that of p58.1+ cells. The results indicate P58 gene mainly expressed in NK, CD8+, CD4+, and CD3+ cells which are consistent with other reports. The ratios of P58+ cells in NK cells were higher than that of CD3+ cells and ratios of P58+ cells in CD8+ cells higher than that of CD4+ cells.3% Polymorphism analysis of the HLA-C binding section of P58: Variers of acids in the areas of P58-HLA-C Binding, Dl and D2, are different from those cDNA reported in Genbank while the basic structures are similarity . The 44 acid of P58 , which specificly recognizing HLA-C, are Lysine (K, Lys), specific for p58.2, Methionine(M,Met) for p58.1 or Asparagine (N, Asn) which haven't confirmed it's specific binding legend. Acid varies of P58 taking place at 40-80, the areas of HLA-C binding. There are two or three patterns of variety at every mutation acid set of different P58 pepites. 2DL1 mutation acid sets at 44 (M-*N) ,49 (L-T) ,52 (A-Q) ,68 (R-P) ,70 (T-~M) , 77 (N-S) ,80 (N-*K) . 2DL2 mutation acid sets at 47 (L-P) ,48 (I-L) ,57(V-S) , 67 (M-K) , 69 (F-T-~M) , 73 (G-A) , 78 (Y-P) , 164 (P-*V) . Mutation acid set of 2DL3 47 (I-A) , 48 (P-H) ,57 (V-A)...
Keywords/Search Tags:killer cell inhibitory receptor, p58, HLA-C, molecular basis
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