Natural Killer Cell Tolerance to Self
自然杀伤细胞对自身的耐受性
基本信息
- 批准号:9433623
- 负责人:
- 金额:$ 52.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-03-01 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptive Cell TransfersAllelesCRISPR/Cas technologyCellsComplexEventEvolutionFamilyGene ClusterGene FamilyGenesGenetic PolymorphismHumanImmuneImpairmentInflammatoryLaboratoriesLeadLectinLicensingMHC Class I GenesMaintenanceMajor Histocompatibility ComplexMalignant NeoplasmsMediatingMolecularMusMutant Strains MiceNK Cell ActivationNatural Killer CellsNormal CellNormal tissue morphologyPathologicProductionReceptor ActivationReceptor CellRegulationRoleSelf ToleranceSiteSpecificitySurveysTestingThinkingTissuesautoreactivitybeta-2 Microglobulincytokinegenome editingkiller immunoglobulin-like receptornovelreceptorreceptor functionresponsetumor
项目摘要
Abstract
Natural killer (NK) cell tolerance to self is incompletely understood despite wide-spread
acceptance of the now familiar “missing-self” hypothesis. Serving as a guiding principle for
several decades, it proposed that NK cells survey tissues for ubiquitously expressed major
histocompatibility complex class I (MHC-I) molecules as self. Normal levels of MHC-I do not
allow NK cell attack but if MHC-I is down-regulated in a pathologic event, NK cells attack. The
applicant and his laboratory discovered the Ly49 family of receptors specific for MHC-I
molecules and that inhibit NK cell activation receptor function, providing a molecular
explanation for the missing-self hypothesis. However, the missing-self hypothesis provides a
few predictions that were not observed, including the hypo-responsiveness of NK cells in
MHC-I-deficient hosts, rather than hyper-reactive NK cells. This can now be explained by more
recent findings from the applicant's laboratory that the Ly49 receptors have a second function to
license or educate NK cells to self-MHC-I, thereby generating appropriate self-tolerant NK cells.
Other unresolved issues regarding missing-self and NK cell tolerance remain unresolved, such
as if all tissues are protected by MHC-I from NK cell attack, the tissues expressing MHC-I that
confer licensing, and if Ly49s are solely responsible for licensing. Herein the applicant proposes
to study NK cell tolerance utilizing novel mice recently generated in his laboratory. In
particular, the Specific Aims of this proposal are to study: 1) Tissue-specificity and temporal
aspects of missing-self protection; 2) Tissue-specific induction and maintenance of licensed NK
cells; and 3) Role of Ly49s in licensing by self-MHC. These studies will enhance our
understanding of NK cell tolerance and the missing-self hypothesis.
摘要
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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Wayne M. Yokoyama其他文献
Immune functions encoded by the natural killer gene complex
自然杀伤基因复合体编码的免疫功能
- DOI:
10.1038/nri1055 - 发表时间:
2003-04-01 - 期刊:
- 影响因子:60.900
- 作者:
Wayne M. Yokoyama;Beatrice F. M. Plougastel - 通讯作者:
Beatrice F. M. Plougastel
The mother-child union: the case of missing-self and protection of the fetus.
母子结合:自我缺失与胎儿保护案例
- DOI:
- 发表时间:
1997 - 期刊:
- 影响因子:11.1
- 作者:
Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Expression of a single inhibitory Ly49 receptor is sufficient to license NK cells for effector functions
单一抑制性 Ly49 受体的表达足以许可 NK 细胞发挥效应功能
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Sytse J. Piersma;Shasha Li;Pamela Wong;Michael D. Bern;Jennifer Poursine‐Laurent;Liping Yang;D. L. Beckman;Bijal A. Parikh;Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Structural basis of MHCI antigen presentation sabotage by cowpox CPXV203
- DOI:
10.1016/j.molimm.2012.02.034 - 发表时间:
2012-05-01 - 期刊:
- 影响因子:
- 作者:
William H. McCoy;Xiaoli Wang;Wayne M. Yokoyama;Ted H. Hansen;Daved Fremont - 通讯作者:
Daved Fremont
Catch us if you can
如果你能就抓住我们
- DOI:
10.1038/419679a - 发表时间:
2002-10-17 - 期刊:
- 影响因子:48.500
- 作者:
Wayne M. Yokoyama - 通讯作者:
Wayne M. Yokoyama
Wayne M. Yokoyama的其他文献
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{{ truncateString('Wayne M. Yokoyama', 18)}}的其他基金
Infectious Disease/Immunology Stimulating Access to Research in Residency (ID/IMM StARR) Program at Washington University
华盛顿大学传染病/免疫学促进住院医师研究 (ID/IMM StARR) 项目
- 批准号:
10592699 - 财政年份:2023
- 资助金额:
$ 52.57万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
10451584 - 财政年份:2018
- 资助金额:
$ 52.57万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
10216997 - 财政年份:2018
- 资助金额:
$ 52.57万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
9980287 - 财政年份:2018
- 资助金额:
$ 52.57万 - 项目类别:
ORIGINS AND FUNCTIONS OF UTERINE NATURAL KILLER CELLS IN PREGNANCY
妊娠期子宫自然杀伤细胞的起源和功能
- 批准号:
9762839 - 财政年份:2018
- 资助金额:
$ 52.57万 - 项目类别:
Natural Killer Cell Control of Murine Cytomegalovirus Infection
自然杀伤细胞控制鼠巨细胞病毒感染
- 批准号:
10444730 - 财政年份:2017
- 资助金额:
$ 52.57万 - 项目类别:














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