NK RECEPTOR FOR HLA CLASS I IN MARROW TRANSPLANTATION

骨髓移植中 HLA I 类的 NK 受体

• 批准号: 6102007
• 负责人: Bo Dupont
• 金额: $ 24.52万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102007
• 关键词: MHC class I antigen; bone marrow transplantation; cell type; clinical research; family genetics; genetic mapping; genotype; graft versus host disease; histocompatibility; homologous transplantation; human subject; leukemia; lymphocyte proliferation; minimal residual disease; molecular cloning; natural killer cells; neoplasm /cancer immunology; neoplasm /cancer relapse /recurrence; nucleic acid sequence; polymerase chain reaction; receptor expression; southern blotting; transplantation immunology

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.

该项目的总体目的是调查角色 同种异体骨髓移植中的天然杀伤（NK）细胞 重点是它们对移植排斥的影响 白血病和白血病复发。 目标是开发DNA 基于杀伤细胞抑制受体的打字系统 （KIR）在NK细胞上表达，并研究如何匹配 这些受体的捐助者和接受者将影响结果 骨髓移植。 KIR是HLA I类的配体 分子和某些KIR介导NK细胞的抑制信号 而其他人则传递激活信号。 目前，40 已经确定了编码KIR的不同cDNA克隆。 这 项目的具体目的是：（i）确定外显子 - 基因组基因的内含子组织并发展基因组 KIR遗传区域的地图。 （ii）开发基于PCR-DNA 由单个KIR基因编码的KIR的打字方法。 （iii）将此键入方法应用于无关的面板 个人和成对的HLA相同兄弟姐妹并执行 单个KIRS的家庭分裂分析。 新的基因 将通过Neucleotide测序来识别和表征 克隆基因。 （iv）开发一种基因特异性RT-PCR方法 检测在NK细胞上表达的单个KIR。 （v）至 确定患者及其骨髓供体的IKR基因型 并确定患者是否经历了移植拒绝，差 嫁接功能或白血病的复发可以区分 没有这些临床事件的患者。 （vi）确定 KIR曲目的重建模式随着它的发展而 转移后的themarrow移植接受者 时期。 该项目应确定是否与Kir匹配 在捐助者和同种异体骨髓移植的接受者之间 影响移植拒绝的风险和最小的风险 残留疾病和白血病复发。 我们将同时 调查KIR曲目的发展 移植期并确定这是否影响 移植结果。