GENETIC COMPLEXITY OF HLA CLASS II GENE REGULATION

HLA II 类基因调控的遗传复杂性

基本信息

  • 批准号:
    2189080
  • 负责人:
  • 金额:
    $ 20.81万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1994
  • 资助国家:
    美国
  • 起止时间:
    1994-05-01 至 1998-04-30
  • 项目状态:
    已结题

项目摘要

Regulation of HLA (human major histocompatibility complex) class II gene expression is the primary focus of investigation in this proposal. HLA Class II antigens are a family of polymorphic surface glycoproteins expressed primarily on B lymphocytes, macrophages, and activated T cells. These antigens are required for the recognition of foreign or altered substances by the immune system. Thus, study of the regulation of these genes is important in understanding the mechanisms that control an immune response and more generally, those that control eukaryotic gene expression. The proposed experiments are a continuation of previous work characterizing defective expression in B cell lines derived from HLA Class II negative congenital immunodeficiency (formerly Bare Lymphocyte Syndrome, BLS) patients. A strategy using insertional mutagenesis with retroviruses to generate new HLA class II negative mutants is outlined. The targets in this approach will be cell lines derived from the parents of BLS patients. Because family studies and earlier analyses from this laboratory indicate that BLS is an autosomal recessive defect, it is assumed that the parental cells contain only one intact and functional copy of a particular regulatory gene. Thus, integration of a proviral genome within or near that wild type regulatory gene should affect its expression and/or function, resulting in lower or absent class II expression allowing selection of the mutant cells. Linkage of the provirus to the putative regulatory gene will allow the isolation of genomic sequences. Subsequently, exons within these flanking regions identified and used to isolate cDNA clones. Characterization and expression of the cDNA clones should reveal clues to the function of these regulatory genes. In addition to promoting the understanding of basic regulatory mechanisms in the immune response, the identification of mutant regulatory genes should lead to gene therapy and long term benefit for BLS patients. Potentially even more important, will be an analysis of regulatory genes in patients with autoimmune diseases in which aberrant expression of HLA class II genes is often found. Furthermore, activation of HLA class II expression in many human malignancies perhaps through the regulatory genes we define may be a significant factor in tumor progression. Understanding the structure and function of HLA class II regulatory genes should provide new strategies to alter HLA class II expression and influence the development of disease.
HLA(人类主要组织相容性复合体)ⅱ类基因的调控

项目成果

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JANET S LEE其他文献

JANET S LEE的其他文献

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{{ truncateString('JANET S LEE', 18)}}的其他基金

GENETIC COMPLEXITY OF HLA CLASS II GENE REGULATION
HLA II 类基因调控的遗传复杂性
  • 批准号:
    2189082
  • 财政年份:
    1994
  • 资助金额:
    $ 20.81万
  • 项目类别:
GENETIC COMPLEXITY OF HLA CLASS II GENE REGULATION
HLA II 类基因调控的遗传复杂性
  • 批准号:
    2189081
  • 财政年份:
    1994
  • 资助金额:
    $ 20.81万
  • 项目类别:
GENETIC COMPLEXITY OF HLA CLASS II GENE REGULATION
HLA II 类基因调控的遗传复杂性
  • 批准号:
    2415240
  • 财政年份:
    1994
  • 资助金额:
    $ 20.81万
  • 项目类别:
HLA CLASS II GENES; REGULATION OF EXPRESSION
HLA II 类基因;
  • 批准号:
    3466894
  • 财政年份:
    1988
  • 资助金额:
    $ 20.81万
  • 项目类别:
HLA CLASS II GENES--REGULATION OF EXPRESSION
HLA II类基因--表达调节
  • 批准号:
    3466893
  • 财政年份:
    1988
  • 资助金额:
    $ 20.81万
  • 项目类别:
HLA CLASS II GENES; REGULATION OF EXPRESSION
HLA II 类基因;
  • 批准号:
    3466896
  • 财政年份:
    1988
  • 资助金额:
    $ 20.81万
  • 项目类别:
HLA CLASS II GENES; REGULATION OF EXPRESSION
HLA II 类基因;
  • 批准号:
    3466895
  • 财政年份:
    1988
  • 资助金额:
    $ 20.81万
  • 项目类别:
HLA CLASS II GENES; REGULATION OF EXPRESSION
HLA II 类基因;
  • 批准号:
    3466897
  • 财政年份:
    1988
  • 资助金额:
    $ 20.81万
  • 项目类别:

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