Role of the Tim-2 Receptor in Immunity and Autoimmunity
Tim-2 受体在免疫和自身免疫中的作用
基本信息
- 批准号:7388778
- 负责人:
- 金额:$ 36.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-07-01 至 2011-03-31
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesAsthmaAutoimmunityB-LymphocytesBindingBlood CirculationBone MarrowCell LineCell Surface ReceptorsCellsChromosomes, Human, Pair 11Chromosomes, Human, Pair 5Cytoplasmic TailDendritic CellsEndocytosisExperimental Autoimmune EncephalomyelitisFamilyFamily memberFerritinFreezingGenerationsGenesH ferritinHematopoieticHepatitis A VirusHumanImmune SeraImmunityImmunoglobulin DomainImmunoglobulinsImmunologistIndividualIntegral Membrane ProteinIronKidneyL-ferritinLaboratoriesLigandsLinkLiverLymphocyteMalpighian corpusclesMolecular CloningMonoclonal AntibodiesMucinsMusNamesPathway interactionsPatternPredispositionRegulationReporterRoleSignal TransductionSpleenStaining methodStainsStromal CellsStructure of germinal center of lymph nodeSurfaceT-LymphocyteTertiary Protein StructureTestingTh2 CellsTissuesTranscriptUrsidae Familybaseexpression cloningimmune functionin vivointerestlymph nodesmacrophagememberrat KIM-1 proteinreceptorselective expressiontissue fixingtraffickinguptake
项目摘要
DESCRIPTION (provided by applicant):
Our proposed studies regard mouse TIM-2, a member of the TIM receptor family. Other members of this family, TIM-1 and TIM-2, are expressed on Th2 and Thl cells, respectively, and regulate T cell immunity and autoimmunity. By developing new antibodies to TIM-2, we have demonstrated that TIM-2 is, in contrast, expressed on all B cells, with the highest expression on germinal center (GC) B cells. Further, we have used molecular cloning to demonstrate that TIM-2 binds to H-ferritin, produced by macrophages. H- and L-ferritin combine to form ferritin, both within cells and in the circulation. Ferritin serves to oxidize and to store iron, but H-ferritin also binds to previously unidentified receptors on lymphocytes, and ferritin is thereby endocytosed. Our studies provide the first identification of a cell-surface receptor for H-ferritin. Based on our results, we propose that TIM-2 regulates immunity, autoimmunity, and germinal center formation. We further propose that H-ferritin initiates transmembrane signaling through TIM-2 and that TIM-2 facilitates the endocytosis of H-ferritin. Finally, we proposed that immunity and GC formation are dependent on ferritin. To test these hypotheses, we propose four specific aims:
Specific Aim 1. Determine the in vivo effect of anti-TIM-2 on immunity and autoimmunity and on germinal center formation
Specific Aim 2. Define the transmembrane signals that are generated by TIM-2 and the structural requirements for their generation.
Specific Aim 3. Define the subcellular localization and trafficking of TIM-2 in lymphocytes, and their relation to the uptake of H-ferritin.
Specific Aim 4. Define the consequences of reduced H-ferritin on immunity and on germinal center formation.
描述(由申请人提供):
我们提出的研究涉及小鼠TIM-2,TIM受体家族的成员。该家族的其他成员TIM-1和TIM-2分别在Th 2和Th 1细胞上表达,并调节T细胞免疫和自身免疫。通过开发针对TIM-2的新抗体,我们已经证明TIM-2相反地在所有B细胞上表达,其中在生发中心(GC)B细胞上表达最高。此外,我们已经使用分子克隆来证明TIM-2与巨噬细胞产生的H-铁蛋白结合。H-和L-铁蛋白在细胞内和循环中结合联合收割机形成铁蛋白。铁蛋白用于氧化和储存铁,但H-铁蛋白也与淋巴细胞上先前未鉴定的受体结合,铁蛋白因此被内吞。我们的研究提供了H-铁蛋白的细胞表面受体的第一个鉴定。基于我们的研究结果,我们提出TIM-2调节免疫、自身免疫和生发中心的形成。我们进一步提出,H-铁蛋白启动跨膜信号通过TIM-2和TIM-2促进H-铁蛋白的内吞作用。最后,我们提出免疫和GC的形成依赖于铁蛋白。为了验证这些假设,我们提出了四个具体目标:
具体目标1.确定抗TIM-2对免疫和自身免疫以及对生发中心形成的体内作用
具体目标2。定义由TIM-2产生的跨膜信号及其产生的结构要求。
具体目标3。定义TIM-2在淋巴细胞中的亚细胞定位和运输,以及它们与H-铁蛋白摄取的关系。
具体目标4。定义H-铁蛋白减少对免疫力和生发中心形成的影响。
项目成果
期刊论文数量(1)
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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William E Seaman其他文献
William E Seaman的其他文献
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{{ truncateString('William E Seaman', 18)}}的其他基金
Role of the Tim-2 Receptor in Immunity and Autoimmunity
Tim-2 受体在免疫和自身免疫中的作用
- 批准号:
6968691 - 财政年份:2005
- 资助金额:
$ 36.89万 - 项目类别:
Role of the Tim-2 Receptor in Immunity and Autoimmunity
Tim-2 受体在免疫和自身免疫中的作用
- 批准号:
7061245 - 财政年份:2005
- 资助金额:
$ 36.89万 - 项目类别:
Role of the Tim-2 Receptor in Immunity and Autoimmunity
Tim-2 受体在免疫和自身免疫中的作用
- 批准号:
7208076 - 财政年份:2005
- 资助金额:
$ 36.89万 - 项目类别:
SHPS-1 As a Regulator of Innate Immunity in Arthritis
SHPS-1 作为关节炎先天免疫的调节剂
- 批准号:
6949037 - 财政年份:2004
- 资助金额:
$ 36.89万 - 项目类别:
SHPS-1 As a Regulator of Innate Immunity in Arthritis
SHPS-1 作为关节炎先天免疫的调节剂
- 批准号:
6839540 - 财政年份:2004
- 资助金额:
$ 36.89万 - 项目类别:
Biology of a New DAP12 Associated Receptor Family
新 DAP12 相关受体家族的生物学
- 批准号:
6330740 - 财政年份:2001
- 资助金额:
$ 36.89万 - 项目类别:
Biology of a New DAP12 Associated Receptor Family
新 DAP12 相关受体家族的生物学
- 批准号:
6633819 - 财政年份:2001
- 资助金额:
$ 36.89万 - 项目类别:
Biology of a New DAP12 Associated Receptor Family
新 DAP12 相关受体家族的生物学
- 批准号:
6722764 - 财政年份:2001
- 资助金额:
$ 36.89万 - 项目类别:
Biology of a New DAP12 Associated Receptor Family
新 DAP12 相关受体家族的生物学
- 批准号:
6514711 - 财政年份:2001
- 资助金额:
$ 36.89万 - 项目类别:
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