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.

该项目的总体目标是研究角色 自然杀伤（NK）细胞在同种异体骨髓移植中的应用 重点关注它们对移植物排斥、残余物的影响 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分型系统 (KIR) 在 NK 细胞上表达并研究如何匹配 这些受体的供体和受体将影响结果 的骨髓移植。 KIR 是 I 类 HLA 的配体 分子和一些 KIR 介导 NK 细胞的抑制信号 而另一些则转换激活信号。 目前，40 已鉴定出编码 KIR 的不同 cDNA 克隆。 这 该项目的具体目标是：（i）确定外显子 基因组 KIR 基因的内含子组织并开发基因组 KIR 遗传区域的图谱。 (ii) 开发基于 PCR-DNA 的 由单个 KIR 基因编码的 KIR 的分型方法。 (iii) 将这种打字方法应用于不相关的面板 个体和成对的 HLA 相同兄弟姐妹并执行 个体 KIR 的家庭隔离分析。 新的KIR基因 将通过核苷酸测序来鉴定和表征 克隆基因。 (iv) 开发基因特异性RT-PCR方法 检测 NK 细胞上表达的单个 KIR。 (v) 至 确定患者及其骨髓捐赠者的 IKR 基因型 并确定患者是否经历移植排斥、贫困 可以区分移植物功能或白血病复发 没有这些临床事件的患者。 (vi) 确定 KIR 指令集的重建模式 移植后的骨髓移植受者 时期。 该项目应确定 KIR 是否匹配 同种异体骨髓移植的供体和受者之间将 影响移植排斥的风险和最小的风险 白血病的残留疾病和复发。 我们将同时 调查后 KIR 曲目的发展 移植期并确定这是否会影响 移植结果。