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
- 来源:
- 关键词:
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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{{ 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:
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