STRUCTURE AND FUNCTION OF THE LYMPHOCYTE FCE RECEPTOR
淋巴细胞 FCE 受体的结构和功能
基本信息
- 批准号:2060755
- 负责人:
- 金额:$ 23.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1989
- 资助国家:美国
- 起止时间:1989-05-01 至 1997-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Investigator's Abstract): This is a continuation
application to study the molecular regulation, structure and function of
the low affinity IgE receptor (Fc-epsilon-RII), using the mouse system.
The overall aim is to gain further insight into the roles this
molecule plays in immediate hypersensitivity and in B-cell activation
and differentiation. In aim number 1 the molecular mechanism of IL-4
induced Fc-epsilon-RII up-regulation will be determined. The promoter
region of the murine Fc-epsilon-RII gene has been tentatively
identified using CAT reporter plasmids. This will be further defined
with additional deletion studies and the region that responds to IL-4
will be determined. The mechanism will then be further explored by
analysis of DNA-binding proteins that may interact with the IL-4
responsive element. Finally, the role that mRNA stabilization plays
in the IL-4- induced Fc-epsilon-RII regulation will also be
determined. In aim number 2, the Fc-epsilon-RII structure necessary for
IgE binding will be determined. Current results indicate that the Fc-
epsilon-RII forms a trimeric structure analogous to other "coiled-coil"
molecules such as tropomyosin. The region responsible for this receptor-
receptor interaction has been identified; it is termed the "stalk"
region of the Fc-epsilon-RII. Additional deletion mutant Fc-epsilon-RII
as well as chimeric Fc-epsilon-RII in which the lectin homologous
region is attached to the other C-type family "stalk" will be prepared
and analyzed for IgE- binding and oligomer formation. A variety of new
biologic activities for the sFc-epsilon-RII have been described in
humans.In aim number 3 the soluble Fc-epsilon-RII constructs prepared
in aim number 2 will be analyzed for biologic activity. The sFc-
epsilon-RII constructs will be tested for activity against mast cells
with respect to mediator and cytokine release and B-cells with respect
to costimulation, IgE production and inhibition of a proptosis.
These studies will also allow the determination of whether a ligand
other than IgE exists for the Fc-epsilon-RII. Two biologic activities
for the intact Fc-epsilon-RII have been identified in the current
grant period--enhancement of antigen presentation and modification
of anti-Ig mediated B-cell activation. Using the mutant Fc-epsilon-RII
molecules produced in aim number 2, the correlation between capacity
for oligomer formation and biologic activity will be determined.In
addition, these mutants, as well as a mutant Fc-epsilon-RII lacking a
cytoplasmic tail will be examined for the capacity to modulate
internalization and cytoskeletal association. Finally, as these
findings indicate new roles for IgE complexes, the effect of in vivo
targeting the Fc-epsilon-RII on TH phenotype will be assayed.
描述(研究者摘要):这是一个延续
应用于研究的分子调控,结构和功能,
低亲和力IgE受体(Fc-γ-RII),使用小鼠系统。
总的目标是进一步深入了解这方面的作用,
分子在速发型超敏反应和B细胞活化中起作用
和差异化。 在目标1中,IL-4的分子机制
确定诱导的Fc-RII-RII上调。启动子
小鼠Fc-γ-RII基因的区域已经被暂时地
使用CAT报告质粒鉴定。 这将进一步明确
通过额外的缺失研究和对IL-4应答的区域
将被确定。 然后将进一步探讨这一机制,
分析可能与IL-4相互作用的DNA结合蛋白
响应元件最后,mRNA稳定化所起的作用
在IL-4诱导的Fc-γ-RII调节中,
测定 在目标2中,制备了用于治疗癌症所必需的Fc-RII-RII结构。
将测定IgE结合。 目前的结果表明,Fc-
ε-RII形成类似于其它“卷曲螺旋”的三聚体结构,
分子如原肌球蛋白。 负责这个受体的区域-
受体相互作用已被确定,它被称为“茎”
Fc-γ-RII区域。额外的缺失突变体Fc-RII-RII
以及嵌合Fc-RII,其中凝集素同源
另一个区域是附着在C型家族的“柄”上的
并分析IgE结合和寡聚体形成。 各种新
sFc-RII-RII的生物活性已在
在目标3中,制备了可溶性Fc-RII-RII构建体,
将分析目标2的生物活性。 sFc-
将测试ε-RII构建体对肥大细胞的活性
在介质和细胞因子释放方面,
共刺激、IgE产生和抑制突眼。
这些研究还将允许确定配体是否
除了IgE之外,对于Fc-γ-RII还存在其它的抗体。两种生物活性
在目前的研究中,
授权期-增强抗原呈递和修饰
抗免疫球蛋白介导的B细胞激活。 使用突变的Fc-γ-RII
目标2中产生的分子,
将测定寡聚体形成和生物活性。
此外,这些突变体,以及缺乏一个或多个氨基酸的突变体Fc-γ-RII,
将检查细胞质尾部调节的能力
内化和细胞骨架结合。 最后,作为这些
研究结果表明,IgE复合物的新作用,体内的影响,
将测定靶向TH表型的Fc-RII-RII。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DANIEL H CONRAD其他文献
DANIEL H CONRAD的其他文献
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{{ truncateString('DANIEL H CONRAD', 18)}}的其他基金
BIACORE 3000 : IMMUNOLOGY, PROTEIN INTERACTIONS STUDIES,; LYME DISEASE
BIACORE 3000:免疫学、蛋白质相互作用研究;
- 批准号:
7166167 - 财政年份:2005
- 资助金额:
$ 23.32万 - 项目类别:
BIACORE 3000 : PROTEIN-NUCLEIC ACID INTERACTIONS, T CRUZI STUDIES
BIACORE 3000:蛋白质-核酸相互作用,T CRUZI 研究
- 批准号:
7166168 - 财政年份:2005
- 资助金额:
$ 23.32万 - 项目类别:
BIACORE 3000 : PROTEIN DRUG INTERACTION STUDIES
BIACORE 3000:蛋白质药物相互作用研究
- 批准号:
7166169 - 财政年份:2005
- 资助金额:
$ 23.32万 - 项目类别:
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