IMMUNOGENETIC STUDIES

免疫遗传学研究

• 批准号: 3268094
• 负责人: Frances E Ward
• 金额: $ 31.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1974
• 资助国家: 美国
• 起止时间: 1974-10-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3268094
• 关键词: African American; B lymphocyte; T lymphocyte; alleles; autosomal recessive trait; biological polymorphism; gene interaction; genetic markers; graft versus host disease; hereditary hemochromatosis; human population genetics; human subject; immunogenetics; leukocyte antigen typing; major histocompatibility complex; monoclonal antibody; neoplasm /cancer genetics; nomenclature; serology /serodiagnosis

The longterm objective of this research plan is to improve our understanding of the genetic specificity of immune recognition and of responses to major and minor histocompatibility antigens and to MHC-restricted antigens. We will use four approaches to determine the extent of serologically detectable genetic polymorphism within the human major histocompatibility complex (MHC): a.) to compare serologic reaction patterns of different ethnic and hybrid populations to identify antigenic variants, b.) to extensively characterize allo, xeno and monoclonal antibodies in order to identify definitive reagents for polymorphic allodeterminants, c.) to investigate whether serologically defined HLA-A and B allodeterminants are also recognized by cytotoxic lymphocytes and d.) to identify serologic and cellular reagents that distinguish different MHC class II subsets. A variety of serologic and cellular approaches will be taken to determine within the human genome, the identify and location of non-MHC linked histocompatibility antigens which induce acute allograft rejection and severe graft versus host disease in recipients of genotypically MHC identical allografts. Family studies will be carried out to confirm the mode of inheritance of new minor and major allodeterminants, and in recombinant families, to map genes within the MHC complex. Evidence for gene complementation leading to specific unresponsiveness in mixed lymphocyte reactions will be sought. We will investigate the genetic bases for significant associations between the MHC complex and certain diseases; namely idiopathic hemochromatosis and malaria. We will extend existing methodology for genetic analyses of human disorders, particularly those with delayed onset and multiple modes of expression, qualities characteristic of many immunologic disorders.

本研究计划的长期目标是改善我们的 了解免疫识别的遗传特异性和 对主要和次要组织相容性抗原的反应 MHC 限制性抗原。 我们将使用四种方法来确定 人类体内血清学可检测的遗传多态性的程度 主要组织相容性复合体 (MHC)：a.) 比较血清学反应 不同种族和混合人群的模式来识别抗原 变体，b.) 广泛表征同种异体、异种和单克隆 抗体以确定多态性的确定试剂 同种异体决定簇，c.) 调查是否有血清学定义的 HLA-A B 同种异体决定簇也被细胞毒性淋巴细胞识别并且 d.) 识别区分不同 MHC 的血清学和细胞试剂 II 类子集。 各种血清学和细胞学方法将 旨在确定人类基因组中的识别和位置 诱导急性同种异体移植的非 MHC 相关组织相容性抗原 受者的排斥反应和严重的移植物抗宿主病 基因型 MHC 相同的同种异体移植物。 将进行家庭研究 确认新的次要和主要同种异体决定因素的遗传模式， 在重组家族中，绘制 MHC 复合体内的基因图谱。 证据 用于基因互补导致混合中的特定无反应 将寻求淋巴细胞反应。 我们将调查遗传基础 MHC 复合体与某些疾病之间存在显着关联； 即特发性血色病和疟疾。 我们将扩展现有的 人类疾病的遗传分析方法，特别是那些 具有延迟发作和多种表达方式、品质 许多免疫疾病的特征。