NK RECEPTOR FOR HLA CLASS I IN MARROW TRANSPLANTATION

这个项目的总体目标是调查 自然杀伤(NK)细胞在异基因骨髓移植中的应用 强调它们对移植物排斥反应的影响，残留物 白血病和白血病复发。我们的目标是开发一种DNA 基于基因芯片的杀伤细胞抑制受体基因分型系统 (KIR)在NK细胞上的表达，并研究如何匹配 这些受体的供者和接受者将影响结果。 骨髓移植。KIRS是人类白细胞抗原I类的配体 分子和某些KIR介导NK细胞的抑制信号 而另一些则传递激活信号。目前，有40人 不同的编码kir的cDNA克隆已经被鉴定。这个 这些项目的具体目标是：(I)确定外显子- 基因组KIR基因的内含子组织与基因组的形成 KIR基因区域的地图。(Ii)发展以聚合酶链式反应-DNA为基础的 单个KIR基因编码的KIR的分型方法。 (Iii)将此打字方法应用于不相关的 单个和成对的人类白细胞抗原完全相同的兄弟姐妹 单项家畜的家族分离分析。新的KIR基因 将通过核苷酸序列测定来鉴定和表征 克隆基因。(4)建立基因特异性RT-PCR方法 检测NK细胞上表达的单个KIR。(V)至 检测患者及其骨髓捐献者的IKR基因 并确定发生移植物排斥反应的患者 白血病的移植物功能或复发可与 没有这些临床事件的患者。(Vi)决定 KIR剧目在#年发展时的重组模式 心脏移植受者在移植后的情况 句号。该项目应确定是否匹配KIR 异基因骨髓移植的捐赠者和接受者之间 影响移植排斥反应的风险，将风险降至最低 残留疾病和白血病复发。我们会同时 调查后KIR剧目的发展- 移植期限并确定这是否会影响 移植结果。

The overall objective of this project is to investigate the role of natural killer (NK) cells in allogeneic marrow transplantation with emphasis on their influence on graft rejection, residual leukemia and leukemia relapse. The goal is to develop a DNA based typing system ofor the Killer Cell Inhibitory Receptors (KIR) expressed on NK cells and to investigate how matching donors and recipients for these receptors will affect the outcome of marrow transplantation. KIRs are ligands for HLA class I molecules and some KIRs mediate inhibitory signals for NK cells while others transduce activating signals. At present, 40 different cDNA clones encoding KIRs have been identified. The specific aims for the projects are: (i) To determine the exon- intron organization of genomic KIR genes and develop a genomic map for the KIR genetic region. (ii) to develop a PCR-DNA based typing method for KIRs encoded by the individual KIR genes. (iii) To apply this typing method to a panel of unrelated individuals and pairs of HLA identical siblings and perform family segragation analysis for individual KIRs. New KIR genes will be identified and characterized by neucleotide sequencing of clones genes. (iv) To develop a gene specific RT-PCR method for detection of individual KIRs expressed on NK cells. (v) To determine the IKR genotype in patients and their marrow donors and determine if patients experiencing graft-rejection, poor graft function or relapse of leukemia can be distinguished from patients without these clinical events. (vi) To determine the pattern of reconstitution of the KIR repertoire as it develops in themarrow transplant recipient during the post-transplantation period. This project should determine if matching for KIR between donors and recipients of allogeneic marrow grafts will affect the risk for graft rejection and the risk for minimal residual disease and relapse of leukemia. We will simultaneously investigate the KIR repertoire development in the post- transplantation period and determine if this influences transplant outcome.