ALTERED N-LINKED OLIGOSACCHARIDES ON IGG IN RHEMATOID ARTHRITIS
ALTERED N-LINKED OLIGOSACCHARIDES ON IGG IN RHEMATOID ARTHRITIS
批准号:
6100675
负责人:
RUSSELL D. SALTER
金额:
$13.94万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-09-01 至 1999-08-31
关键词:
MHC class II antigen T lymphocyte clinical research crosslink dendritic cells electron microscopy human subject immune tolerance /unresponsiveness immunoglobulin G immunoglobulin isotypes inflammation intracellular transport lymphocyte proliferation oligosaccharides receptor binding rheumatoid arthritis
中文摘要
导致滑膜破坏的慢性炎症反应
组织是类风湿性关节炎(RA)的特征,
病因不明的疾病。 关节中的树突细胞很可能
通过呈递肽在引发疾病中起关键作用
从自身蛋白衍生的抗原到自身反应性T细胞。 我们
已经观察到带有IgG的树突状细胞的摄取增加
改变的N-寡糖,先前显示存在于
RA患者血清和关节滑液中。 这表明
被树突细胞摄取的修饰的IgG(G 0 IgG)可以是
通过II类组织相容性蛋白进行加工和呈递,
有效地,导致T细胞反应性耐受性的破坏,
与IgG衍生的肽。 进一步表征G 0的结合
IgG对树突状细胞的作用,并测试IgG反应性T细胞是否可能
我们将采取以下措施
实验 在具体目标1中,将开发新的测定法
其提供了检测G 0结合的高度灵敏的手段
免疫球蛋白G致树突状细胞。 IgG同种型也将作为
约束力的决定因素 内化Go的亚细胞定位
IgG将使用电子显微镜测定,
G 0 IgG与II类组织相容性处理途径
使用生物化学测定进行评估。 在具体目标2中,
负责结合G 0 IgG的树突状细胞的表面将
用化学交联和凝胶电泳鉴定
分析。 在具体目标3中,来自患者和正常人的T细胞
对照将测试对树突细胞的增殖反应
用G 0 IgG脉冲。 这些实验应该确定G 0
由树突细胞摄取的IgG可以被有效地加工,
通过II类组织相容性分子呈递给外周T细胞
潜在的自体反应细胞。
英文摘要
Chronic inflammatory responses leading to destruction of synovial
tissue is characteristic of rheumatoid arthritis (RA), an autoimmune
disease of unknown etiology. Dendritic cells in the joint are likely
to play a crucial role in initiating the disease by presenting peptide
antigens derived from self proteins to autoreactive T cells. We
have observed increased uptake by dendritic cells of IgGs bearing
altered N-oligosaccharides, shown previously to be present in the
serum and synovial fluid of RA patients. This suggests that
modified IgG (G0 IgG) taken up by dendritic cells may be
processed and presented via class II histocompatibility proteins quite
efficiently, leading to a breakdown in tolerance of T cells reactive
with IgG-derived peptides. To further characterize binding of G0
IgG to dendritic cells and test whether IgG-reactive T cells might
contribute to the disease, we will perform the following
experiments. In specific aim 1, novel assays will be developed
which provide a highly sensitive means of detecting binding of G0
IgG to dendritic cells. IgG isotype will also be tested as a
determinant of binding. Subcellular localization of internalized Go
IgG will determined using electron microscopy, and intersection of
G0 IgG with the class II h istocompatibiity processing pathway
assessed using biochemical assays. In specific aim 2, receptors on
the surface of dendritic cells responsible for binding G0 IgG will be
identified using chemical crosslinking and gel electrophoretic
analyses. In specific aim 3, T cells from patients and normal
controls will be tested for proliferative responses to dendritic cells
pulsed with G0 IgG. These experiments should determine if G0
IgG taken up by dendritic cells can be efficiently processed and
presented via class II histocompatibility molecules to peripheral T
cells which are potentially autoreactive.
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会议论文
Interaction of microvesicles and bacterial toxins with immune cells
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批准号:7447395
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项目类别:
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资助金额:$35.87万
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财政年份:2007
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负责人:RUSSELL D. SALTER
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依托单位:
Interaction of microvesicles and bacterial toxins with immune cells
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批准号:7881640
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项目类别:
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资助金额:$35.51万
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财政年份:2007
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负责人:RUSSELL D. SALTER
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依托单位:
Interaction of microvesicles and bacterial toxins with immune cells
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批准号:8091345
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项目类别:
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资助金额:$35.16万
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财政年份:2007
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负责人:RUSSELL D. SALTER
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依托单位:
Interaction of microvesicles and bacterial toxins with immune cells
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批准号:7626804
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项目类别:
-
资助金额:$35.87万
-
财政年份:2007
-
负责人:RUSSELL D. SALTER
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依托单位:
Interaction of microvesicles and bacterial toxins with immune cells
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批准号:7314444
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项目类别:
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资助金额:$36.57万
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财政年份:2007
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负责人:RUSSELL D. SALTER
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依托单位:
FUNCTION OF DISTINCT DC SUBSETS IN RHESUS MODEL
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批准号:6989521
-
项目类别:
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资助金额:$16.7万
-
财政年份:2004
-
负责人:RUSSELL D. SALTER
-
依托单位:
Ig-Reactive T Cells in Rheumatoid Arthritis
-
批准号:6561896
-
项目类别:
-
资助金额:$7.48万
-
财政年份:2002
-
负责人:RUSSELL D. SALTER
-
依托单位:
Ig-Reactive T Cells in Rheumatoid Arthritis
-
批准号:6665074
-
项目类别:
-
资助金额:$7.48万
-
财政年份:2002
-
负责人:RUSSELL D. SALTER
-
依托单位:
CALNEXIN AND CLASS I MHC FUNCTION
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批准号:2004608
-
项目类别:
-
资助金额:$19.33万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
CALNEXIN AND CLASS I MHC FUNCTION
-
批准号:2887156
-
项目类别:
-
资助金额:$20.43万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
CALNEXIN AND CLASS I MHC FUNCTION
-
批准号:2672712
-
项目类别:
-
资助金额:$19.85万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
CALNEXIN AND CLASS I MHC FUNCTION
-
批准号:6373516
-
项目类别:
-
资助金额:$21.67万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
CALNEXIN AND CLASS I MHC FUNCTION
-
批准号:6170132
-
项目类别:
-
资助金额:$21.04万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
ALTERED N-LINKED OLIGOSACCHARIDES ON IGG IN RHEMATOID ARTHRITIS
-
批准号:6235881
-
项目类别:
-
资助金额:$14.08万
-
财政年份:1997
-
负责人:RUSSELL D. SALTER
-
依托单位:
Function of Distinct Dendritic Cell Subsets In a Rhesus Model
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批准号:7643414
-
项目类别:
-
资助金额:$28.31万
-
财政年份:--
-
负责人:RUSSELL D. SALTER
-
依托单位:
FUNCTION OF DISTINCT DC SUBSETS IN RHESUS MODEL
-
批准号:7257095
-
项目类别:
-
资助金额:$17.71万
-
财政年份:--
-
负责人:RUSSELL D. SALTER
-
依托单位:
FUNCTION OF DISTINCT DC SUBSETS IN RHESUS MODEL
-
批准号:7091995
-
项目类别:
-
资助金额:$17.2万
-
财政年份:--
-
负责人:RUSSELL D. SALTER
-
依托单位:
Function of Distinct Dendritic Cell Subsets In a Rhesus Model
-
批准号:7478056
-
项目类别:
-
资助金额:$28.32万
-
财政年份:--
-
负责人:RUSSELL D. SALTER
-
依托单位:
海外基金