Regulation of Human IELs by CD94 and HLA-E

CD94 和 HLA-E 对人类 IEL 的调节

基本信息

  • 批准号:
    6916232
  • 负责人:
  • 金额:
    $ 26.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-09-01 至 2006-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Applicant's Abstract): In the microenvironment of the human gut epithelium, armed effector T cells (T-IELs) with cytolytic functions are tightly regulated by CD94/NKG2, a novel family of HLA-E specific heterodimeric receptors originally identified on NK cells. These receptors can switch adaptive responses on and off by using different activating or inhibitory NKG2 isotypes and appear to regulate remarkably large T-IEL clonal expansions in healthy individuals. In celiac disease, a condition associated with epithelial damage, they exclusively express activating isotypes, suggesting that dysregulation causes disease. The overarching goal of the proposed research is to develop a model of how adaptive immunity mediated by cytolytic effector T cells is regulated in the gut microenvironment by CD94/NKG2 receptors of innate immunity. The investigator will focus on three specific aims fundamental to understanding the biological significance of this regulatory system. In Specific Aim 1, expression and regulation of HLA-E and G on intestinal epithelial cells, cytokines produced in the GALT in normal and inflammatory conditions will be used to stimulate expression of HLA-E and G by freshly isolated IECs, IEC lines and professional APCs. In Specific Aim 2, expression and regulation of CD94/NKG2 isotypes by T-IELs, the investigator will characterize the pattern of expression of the different CD94/NKG2 isotypes, the TCR V-beta and V-alpha repertoire of T-IELs expressing distinct CD94/NKG2 isotypes (by spectroanalysis and sequencing), and the cytokine profile of T-IELs expressing distinct CD94/NKG2 isotypes. In Specific Aim 3, functional properties of CD94INKG2 receptors expressed by T-IELs, cloned T-IELs expressing single NKG2 isotypes will be used to determine how they contribute to cytolytic function and cytokine secretion and to characterize the biochemical signals involved. The proposed research will test in a molecularly well-defined system the general hypothesis that NK receptors and non-classical MHC class I-like molecules regulate interactions between T-IELs and intestinal epithelial cells. The results are likely to have important implications for our understanding of the processes that fine tune cytolytic T cell responses in the high antigen environment of the gut, regulating local immunity and controlling epithelial cell damage.
描述(申请人摘要):在人体肠道的微环境中

项目成果

期刊论文数量(0)
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BANA JABRI其他文献

BANA JABRI的其他文献

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{{ truncateString('BANA JABRI', 18)}}的其他基金

Localizing Pathogenically Relevant Transglutaminase 2 in Celiac Disease
乳糜泻中致病相关转谷氨酰胺酶 2 的定位
  • 批准号:
    10704104
  • 财政年份:
    2021
  • 资助金额:
    $ 26.69万
  • 项目类别:
Localizing Pathogenically Relevant Transglutaminase 2 in Celiac Disease
乳糜泻中致病相关转谷氨酰胺酶 2 的定位
  • 批准号:
    10296119
  • 财政年份:
    2021
  • 资助金额:
    $ 26.69万
  • 项目类别:
Localizing Pathogenically Relevant Transglutaminase 2 in Celiac Disease
乳糜泻中致病相关转谷氨酰胺酶 2 的定位
  • 批准号:
    10483182
  • 财政年份:
    2021
  • 资助金额:
    $ 26.69万
  • 项目类别:
GATA4 as a window into the link between metabolism and immunity
GATA4 作为代谢与免疫之间联系的窗口
  • 批准号:
    8570897
  • 财政年份:
    2013
  • 资助金额:
    $ 26.69万
  • 项目类别:
GATA4 as a window into the link between metabolism and immunity
GATA4 作为代谢与免疫之间联系的窗口
  • 批准号:
    8715690
  • 财政年份:
    2013
  • 资助金额:
    $ 26.69万
  • 项目类别:
Innate and adaptive immunity in celiac disease
乳糜泻的先天性和适应性免疫
  • 批准号:
    8727526
  • 财政年份:
    2005
  • 资助金额:
    $ 26.69万
  • 项目类别:
Innate and adaptive immunity in celiac disease
乳糜泻的先天性和适应性免疫
  • 批准号:
    8528559
  • 财政年份:
    2005
  • 资助金额:
    $ 26.69万
  • 项目类别:
IEL and NKG2 Receptors in Celiac Disease
IEL 和 NKG2 受体在乳糜泻中的作用
  • 批准号:
    7120637
  • 财政年份:
    2005
  • 资助金额:
    $ 26.69万
  • 项目类别:
IEL and NKG2 Receptors in Celiac Disease
IEL 和 NKG2 受体在乳糜泻中的作用
  • 批准号:
    7485761
  • 财政年份:
    2005
  • 资助金额:
    $ 26.69万
  • 项目类别:
IEL and NKG2 Receptors in Celiac Disease
IEL 和 NKG2 受体在乳糜泻中的作用
  • 批准号:
    7677961
  • 财政年份:
    2005
  • 资助金额:
    $ 26.69万
  • 项目类别:

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