HLA-Releasing Metalloproteinase in Allograft Rejection
HLA-Releasing Metalloproteinase in Allograft Rejection
批准号:
7769785
负责人:
YURI BUSHKIN
金额:
$32.77万
依托单位国家:
美国
项目类别:
财政年份:
2005
资助国家:
美国
项目状态:
已结题
起止时间:
2005-03-01 至 2012-02-28
关键词:
Adam15 geneAddressAllogenicAllograftingAlternative SplicingAntigen PresentationAvidityBiological AssayCD8B1 geneCell LineCellsChimera organismChimeric ProteinsCleaved cellCoculture TechniquesComplexCytomegalovirusDNA Microarray ChipDataDelayed HypersensitivityDisintegrinsEndothelial CellsEnzymesExpression LibraryFamily memberFibroblastsGenesGoalsGranulocyte-Macrophage Colony-Stimulating FactorHLA-A2 AntigenHomologous GeneHumanImmuneInfectionInterferon Type IIInterferonsLinkMajor Histocompatibility ComplexMeasuresMediatingMetalloproteasesMicroarray AnalysisModelingMonoclonal AntibodiesMusPathway interactionsPeptidesPeripheral Blood Mononuclear CellPhysiologicalProcessProteinsRegulationRoleScreening procedureSiteSmall Interfering RNAStimulusSubstrate InteractionSurfaceSystemT-LymphocyteTestingTissuesTransmembrane DomainTransplantationTransplantation Toleranceblastomere structurecytokinedesignenzyme activityenzyme substrateextracellularin vivoinhibitor/antagonistleukemiamonocytemutantnoveloverexpressionresponse
中文摘要
我们之前已经描述了金属蛋白酶介导的可溶性MHC I类释放途径
英文摘要
We have previously described the metalloproteinase-mediated pathway of soluble MHC class I release
and proposed its role in transplantation. We found that the release of soluble MHC class I is mediated by a
disintegrin and metalloprotease family member, ADAM17. Endothelial cells (EC) co-cultured with
allogeneic T cells up-regulate specific activation markers and both the expression and activity of ADAM 17.
This activation is driven by interferon-gamma and culminates in the release of soluble MHC class I proteins
by EC. However, at least one other metalloproteinase distinct from ADAM17 is fully capable of releasing
soluble MHC class I. Its activity may be regulated by cytokines in a tissue-specific manner. Screening of a
human leukemia expression library with our mAb that blocks the release of soluble MHC class I led to
identification of a novel protein BC036469 with yet unknown function. This ubiquitously expressed protein
may participate in the mechanism of soluble MHC class I release by mediating specific enzyme/substrate
interactions and its function may be regulated by cell-specific cytokines in different tissues. Three
independent aims are designed to address these questions. First, we will identify cytokine-inducible
metalloproteinases capable of processing MHC class I by using a panel of ADAM-deficient cell lines and by
DNA microarray analysis. Second, the function of BC036469 protein will be determined by overexpressing
wild-type and deletion mutants, and by disrupting expression of the endogenous protein with specific
siRNA. Finally, we will determine the sites required for productive enzyme/substrate interactions within
alpha 3 and transmembrane domains of MHC class I and test the ability of specific peptides to inhibit the
interaction. The predicted role of soluble MHC class I in antigen presentation will be tested using the trans-
vivo delayed-type hypersensitivity assay in the linked suppression model of immune regulation by HLA-A2-
restricted CD8 low avidity T regulator cells controlling transplantation tolerance.
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Rapid Analysis of Single T Cell Immunity Signatures in Tuberculosis
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批准号:8706329
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项目类别:
-
资助金额:$37.96万
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财政年份:2013
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负责人:YURI BUSHKIN
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依托单位:
Rapid Analysis of Single T Cell Immunity Signatures in Tuberculosis
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批准号:8721333
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项目类别:
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资助金额:$74.98万
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财政年份:2012
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负责人:YURI BUSHKIN
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依托单位:
Rapid Analysis of Single T Cell Immunity Signatures in Tuberculosis
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批准号:8541693
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项目类别:
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资助金额:$72.72万
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财政年份:2012
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负责人:YURI BUSHKIN
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依托单位:
Rapid Analysis of Single T Cell Immunity Signatures in Tuberculosis
-
批准号:8414032
-
项目类别:
-
资助金额:$37.0万
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财政年份:2012
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负责人:YURI BUSHKIN
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依托单位:
HLA-Releasing Metalloproteinase in Allograft Rejection
-
批准号:7923507
-
项目类别:
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资助金额:$29.49万
-
财政年份:2009
-
负责人:YURI BUSHKIN
-
依托单位:
Novel targets for vaccines against tuberculosis
-
批准号:6859051
-
项目类别:
-
资助金额:$23.34万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
Novel targets for vaccines against tuberculosis
-
批准号:7386290
-
项目类别:
-
资助金额:$18.98万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-Releasing Metalloproteinase in Allograft Rejection
-
批准号:6871672
-
项目类别:
-
资助金额:$31.12万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-Releasing Metalloproteinase in Allograft Rejection
-
批准号:7454961
-
项目类别:
-
资助金额:$32.77万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-Releasing Metalloproteinase in Allograft Rejection
-
批准号:7373536
-
项目类别:
-
资助金额:$32.95万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-Releasing Metalloproteinase in Allograft Rejection
-
批准号:7025818
-
项目类别:
-
资助金额:$32.68万
-
财政年份:2005
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-RELEASING METALLOPROTEINASE IN ALLOGRAFT REJECTION
-
批准号:6374208
-
项目类别:
-
资助金额:$24.0万
-
财政年份:1999
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-RELEASING METALLOPROTEINASE IN ALLOGRAFT REJECTION
-
批准号:6170396
-
项目类别:
-
资助金额:$23.3万
-
财政年份:1999
-
负责人:YURI BUSHKIN
-
依托单位:
HLA-RELEASING METALLOPROTEINASE IN ALLOGRAFT REJECTION
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批准号:2892534
-
项目类别:
-
资助金额:$22.62万
-
财政年份:1999
-
负责人:YURI BUSHKIN
-
依托单位:
CD8+ T CELL RESPONSE IN RESISTANCE TO TUBERCULOSIS
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批准号:2771660
-
项目类别:
-
资助金额:$24.15万
-
财政年份:1997
-
负责人:YURI BUSHKIN
-
依托单位:
CD8+ T CELL RESPONSE IN RESISTANCE TO TUBERCULOSIS
-
批准号:6389838
-
项目类别:
-
资助金额:$23.64万
-
财政年份:1997
-
负责人:YURI BUSHKIN
-
依托单位:
CD8+ T CELL RESPONSE IN RESISTANCE TO TUBERCULOSIS
-
批准号:2541555
-
项目类别:
-
资助金额:$24.15万
-
财政年份:1997
-
负责人:YURI BUSHKIN
-
依托单位:
CD8+ T CELL RESPONSE IN RESISTANCE TO TUBERCULOSIS
-
批准号:6183930
-
项目类别:
-
资助金额:$23.64万
-
财政年份:1997
-
负责人:YURI BUSHKIN
-
依托单位:
CD8+ T CELL RESPONSE IN RESISTANCE TO TUBERCULOSIS
-
批准号:6056508
-
项目类别:
-
资助金额:$24.13万
-
财政年份:1997
-
负责人:YURI BUSHKIN
-
依托单位:
T CELL RECEPTOR-LIKE/T8/HLA INTERACTIONS IN RECOGNITION
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批准号:3190487
-
项目类别:
-
资助金额:$15.91万
-
财政年份:1987
-
负责人:YURI BUSHKIN
-
依托单位:
海外基金