Investigation into the Endogenous Ligand Repertoire of the Non-Classical MHC-Related Protein, MR1 in Multiple Myeloma Cell Lines
多发性骨髓瘤细胞系中非经典 MHC 相关蛋白 MR1 内源配体库的研究
基本信息
- 批准号:10452305
- 负责人:
- 金额:$ 23.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAntigen PresentationAntigensBindingBiochemicalBiochemistryBiological AssayBlood CirculationBlood donorBlood specimenCancer cell lineCancerousCatalogsCell LineCell surfaceCellsChemical StructureChemicalsClone CellsCollaborationsComplexDevelopmentDiseaseFolic AcidFolic Acid DerivativeFutureGenetic TranscriptionGenomicsGoalsHealth SciencesHumanImmuneImmunotherapyIndividualInfectionInvestigationLeadLigand BindingLigandsLightMHC antigenMajor Histocompatibility ComplexMalignant NeoplasmsMetabolic PathwayModelingMolecularMucous MembraneMultiple MyelomaNatural ProductsNatureOklahomaPathway interactionsPatientsPeptidesPhenotypePlasma CellsPlayPopulationPositioning AttributePropertyProteinsProtocols documentationReagentRecombinantsRecording of previous eventsReportingResearchRiboflavinRoleStainsSurfaceT-Cell Receptor GenesT-LymphocyteT-cell receptor repertoireTRANCE proteinTechniquesTestingTissuesTumor AntigensUniversitiesUrsidae FamilyWorkadaptive immunityalpha-beta T-Cell Receptorbasebiobankcancer cellcancer typecytokinecytotoxicexhaustionexperimental studyinnovative technologiesinterestmetabolomemicrobialmicroorganism antigenneoplastic cellnovelpathogenresponsesensorsequencing platformsmall moleculesocialstructural biologytumor
项目摘要
Project Abstract:
Major Histocompatibility Complex (MHC) molecules have been long been appreciated as the bridge between
the innate and adaptive immune cell populations. Beyond the peptide-presenting classical MHC class I and II
molecules, there exists a variety of other structurally related proteins in humans that have been found to present
diverse antigen types to a variety of T cell sub-types. Among these is the monomorphic MHC-related protein 1
(MR1) which is historically known for the presentation of microbially-derived riboflavin metabolites to Mucosal-
Associated Invariant T (MAIT) cells. Expanding on this initial observation, our group and others have shown that
the ligandome of MR1 is much more diverse than previously appreciated. MR1 is capable of presenting ligands
of various sizes and chemical structures beyond the originally described ribityl metabolites to a vast array of
MR1-restricted T cells (MR1Ts) carrying fully rearranged αβ TCRs. Recently, there have been emerging reports
of MR1T clones that have shown MR1-dependent cytotoxic activity against cancerous tissues in the complete
absence of any microbial infection or microbial ligands. Due to the unprecedented nature of these observations
and the potential impact of an MR1-based immunotherapy, it is important that the ligands being presented by
MR1 in the context of cancer-induced cellular disfunction be identified. Taking into consideration our own
research and these novel reports, we propose that MR1 acts as a sensor of the cellular metabolome in both the
context of microbial infection and endogenous disfunction like cancer, presenting a diverse array of metabolite
antigens. Due to our established track record investigating the biochemistry of MR1 and our existing collaborative
ligand discovery pipeline for MR1, The Adams Lab is uniquely poised to investigate the identity of the antigens
that MR1 is presenting in the context of cancer. Our investigation will focus on the plasma cell cancer, multiple
myeloma, as cell lines of this cancer have been shown to have abnormally high expression of MR1 at the cell
surface, indicating a higher possible antigenic load. We propose that our established microbial-ligand discovery
pipeline for MR1 can be adapted to investigate the tumor associated antigens (TAAs) being presented on the
surface of myeloma cells by either expressing our MR1 construct directly in these cell lines or by adding their
lysate into the media of transfected producing cells; both techniques that we have used before. Identification of
the ligands loaded into MR1 from these experiments will be determined by LC-MS/MS through our collaboration
with the Hildebrand Lab at the Oklahoma University Health Sciences Center. Following this determination, we
will capitalize on our structural biology expertise to determine how potential ligands bind the MR1 pocket. Finally,
we will use MR1/TAA tetramers to stain MR1T clones from donor blood samples and investigate their
transcriptional phenotype to shed light on the cognate T cell population that is reactive to these antigens.
项目简介:
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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Erin June Adams其他文献
Erin June Adams的其他文献
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{{ truncateString('Erin June Adams', 18)}}的其他基金
Investigation into the Endogenous Ligand Repertoire of the Non-Classical MHC-Related Protein, MR1 in Multiple Myeloma Cell Lines
多发性骨髓瘤细胞系中非经典 MHC 相关蛋白 MR1 内源配体库的研究
- 批准号:
10557884 - 财政年份:2022
- 资助金额:
$ 23.86万 - 项目类别:
Molecular and functional investigation of the role of HLA-F in immune regulation
HLA-F在免疫调节中作用的分子和功能研究
- 批准号:
10503676 - 财政年份:2022
- 资助金额:
$ 23.86万 - 项目类别:
Molecular and functional investigation of the role of HLA-F in immune regulation
HLA-F在免疫调节中作用的分子和功能研究
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10636894 - 财政年份:2022
- 资助金额:
$ 23.86万 - 项目类别:
Determining the Origins of Nonclassical Class I molecules through Molecular and Functional Approaches
通过分子和功能方法确定非经典 I 类分子的起源
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10501472 - 财政年份:2022
- 资助金额:
$ 23.86万 - 项目类别:
Determining the Origins of Nonclassical Class I molecules through Molecular and Functional Approaches
通过分子和功能方法确定非经典 I 类分子的起源
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10645114 - 财政年份:2022
- 资助金额:
$ 23.86万 - 项目类别:
Facility and Building System Upgrades Support for the Howard T. Ricketts Biocontainment Laboratory
为 Howard T. Ricketts 生物防护实验室提供设施和建筑系统升级支持
- 批准号:
10394614 - 财政年份:2021
- 资助金额:
$ 23.86万 - 项目类别:
Facility and Building System Upgrades Support for the Howard T. Ricketts Biocontainment Laboratory
为 Howard T. Ricketts 生物防护实验室提供设施和建筑系统升级支持
- 批准号:
10631368 - 财政年份:2021
- 资助金额:
$ 23.86万 - 项目类别:
Molecular and functional investigation of the role of CD1 in gamma delta T cell surveillance
CD1 在 γ δ T 细胞监测中作用的分子和功能研究
- 批准号:
10670830 - 财政年份:2020
- 资助金额:
$ 23.86万 - 项目类别:
Molecular and functional investigation of the role of CD1 in gamma delta T cell surveillance
CD1 在 γ δ T 细胞监测中作用的分子和功能研究
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10268214 - 财政年份:2020
- 资助金额:
$ 23.86万 - 项目类别:
Molecular and functional investigation of the role of CD1 in gamma delta T cell surveillance
CD1 在 γ δ T 细胞监测中作用的分子和功能研究
- 批准号:
10462661 - 财政年份:2020
- 资助金额:
$ 23.86万 - 项目类别:
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