LJI Epitope Validation Center: Characterization of epitope-specific T cells responding to food, fungal and inner city allergens
LJI Epitope Validation Center: Characterization of epitope-specific T cells responding to food, fungal and inner city allergens
批准号:
10321619
负责人:
Alessandro Sette
金额:
$115.36万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-01-01 至 2022-12-31
关键词:
AddressAdultAllergen ImmunotherapyAllergensAllergicAllergic DiseaseAlternariaAntigensAspergillusAsthmaBiological AssayCD4 Positive T LymphocytesCattleCellsCharacteristicsChildChildhoodChildhood AsthmaClinicalCollaborationsConsumptionDevelopmentDiagnosticDictyopteraDiseaseEpitopesEvolutionExposure toFlow CytometryFoodFood HypersensitivityFood Protein-Induced Enterocolitis SyndromeFundingGene Expression ProfileGeneticGerman populationGoalsHouseholdHypersensitivityImmune responseIndividualInfantInhalationInterleukin-17Interleukin-5InvestigationMeasurementMessenger RNAMilkMilk HypersensitivityModalityMolecularMolecular ProfilingMusNational Institute of Allergy and Infectious DiseaseNoseOccupational ExposureOralPatientsPersonsPhenotypeProductionProteinsSamplingSampling StudiesSeveritiesSeverity of illnessSourceSpecificitySpecimenSputumSystemT cell receptor repertoire sequencingT cell responseT-LymphocyteT-cell receptor repertoireTargeted ResearchTeenagersTherapeuticTimeUp-RegulationValidationWood materialWorkantigen-specific T cellsasthmaticbaseclinical phenotypeclinical practicecockroach allergencohortcomparativecytokinedesensitizationdiagnostic valueenzyme linked immunospot assayfood allergenhigh riskimprovedinner cityinsightlongitudinal analysismouse allergennovel diagnosticsnovel therapeutic interventionprogramsprospectiveresponsesingle-cell RNA sequencingsynergismtranscriptome sequencingurban setting
中文摘要
中心计划摘要/摘要
我们的建议将使用表位来比较评估三种不同原型的免疫反应
过敏性疾病。我们将研究蟑螂(CR)和老鼠(MO)吸入性过敏原,它们与
随着市中心儿童哮喘的发展(项目1);牛奶(CM)是最普遍的
公认的儿科食物过敏原(项目2);曲霉菌(ASP)和交链孢霉(ALT)真菌过敏原,
它们与严重形式的哮喘有关(项目3)。广泛的科学重叠将提供
项目之间协同增效的机会。我们的研究广泛地利用了由
NIAID,以进一步扩大调查的协同作用和影响。应对措施的演变将是
在自然暴露、作为工作职责一部分的暴露和过敏原之后的时间函数检查
免疫疗法(AIT)。我们还将研究和比较接触过病毒但仍保持健康的个人,以
有轻度过敏和严重哮喘的人。我们的假设是,这些不同的群体
可以根据他们的T细胞反应来区分。具体地说,不同的群体可能会认识到
不同的蛋白质过敏原或片段(表位)。也有可能蛋白质和遗传程序
在不同类型和严重程度的过敏性疾病中看到的T细胞(T细胞表型)的特征将是
独一无二。我们的附加假设是T细胞表型的进化可以让我们深入了解
过敏性和哮喘的发病机制。如果是这样的话,它将具有潜在的诊断能力
价值,并可能提出新的治疗干预措施。
英文摘要
CENTER PROGRAM SUMMARY/ABSTRACT
Our proposal will use epitopes to comparatively evaluate immune responses in three different prototypic
allergic diseases. We will study cockroach (CR) and mouse (MO) inhalation allergens, which are associated
with the development of asthma in inner city children (Project 1); cow’s milk (CM), the most prevalently
recognized pediatric food allergen (Project 2); and Aspergillus (ASP) and Alternaria (ALT) fungal allergens,
which are associated with severe forms of asthma (Project 3). The extensive scientific overlap will offer
opportunities for synergies between projects. Our study extensively utilizes cohorts independently funded by
NIAID, to further multiply synergies and impact of the investigations. The evolution of responses will be
examined as a function of time following natural exposure, exposure as part of work-duties and allergen
immunotherapy (AIT). We will also study and compare individuals that are exposed but remain healthy, to
people that have mild allergies and those that have severe asthma. Our hypothesis is that these distinct groups
can be distinguished on the basis of their T cell response. Specifically, different groups might recognize
different protein allergens or fragments (epitopes). It is also possible that the protein and genetic programs
characteristic of T cells (T cell phenotypes) seen in allergic diseases of different types and severity will be
unique. Our additional hypotheses are that evolution of T cell phenotypes can give us insights into the
mechanism of allergic and asthmatic disease. If this were to be the case, it would have potential diagnostic
value, and possibly suggest new therapeutic interventions.
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DOI:
10.3389/fimmu.2018.00886
发表时间:
2018
期刊:
Frontiers in immunology
影响因子:
7.3
作者:
[da Silva Antunes R, Pham J, McMurtrey C, Hildebrand WH, Phillips E, Mallal S, Sidney J, Busse P, Peters B, Schulten V, Sette A]
通讯作者:
Sette A
Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity.
德国蟑螂提取物中的过敏原含量和对一组新扩张的蟑螂过敏原的敏化曲线决定了IgE反应性的体外提取效力。
DOI:
10.1016/j.jaci.2018.07.036
发表时间:
2019-04
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
作者:
[Glesner J, Filep S, Vailes LD, Wünschmann S, Chapman MD, Birrueta G, Frazier A, Jeong KY, Schal C, Bacharier L, Beigelman A, Busse P, Schulten V, Sette A, Pomés A]
通讯作者:
Pomés A
The association of allergic sensitization patterns in early childhood with disease manifestations and immunological reactivity at 10 years of age.
儿童早期过敏致敏模式与 10 岁时疾病表现和免疫反应性的关联。
DOI:
10.1111/cea.13406
发表时间:
2019
期刊:
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子:
--
作者:
[Schulten,Véronique, Frazier,April, Calatroni,Agustin, Kattan,Meyer, Bacharier,LeonardB, O'Connor,GeorgeT, Sandel,MeganT, Wood,RobertA, Wheatley,LisaM, Togias,Alkis, Visness,CynthiaM, Dresen,Amy, Gern,JamesE, Sette,Alessandro]
通讯作者:
Sette,Alessandro
Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma.
过敏和哮喘中小鼠特异性 T 细胞反应的过敏原和表位靶标。
DOI:
10.3389/fimmu.2018.00235
发表时间:
2018
期刊:
Frontiers in immunology
影响因子:
7.3
作者:
[Schulten,Véronique, Westernberg,Luise, Birrueta,Giovanni, Sidney,John, Paul,Sinu, Busse,Paula, Peters,Bjoern, Sette,Alessandro]
通讯作者:
Sette,Alessandro
DOI:
10.1016/j.crmeth.2022.100350
发表时间:
2022-12-19
期刊:
Cell reports methods
影响因子:
--
作者:
[]
通讯作者:
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Human immune signatures of Dengue virus and Mycobacterium Tuberculosis exposure in infection, disease and vaccination
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