A mouse to track dual TCR T cells

追踪双 TCR T 细胞的小鼠

基本信息

  • 批准号:
    8563789
  • 负责人:
  • 金额:
    $ 7.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-05-15 至 2015-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Allelic exclusion ensures that most T and B lymphocytes express only one antigen receptor specificity - a central tenet of clonal selection theory. The discovery that some T and B cells in normal mice and humans express two different antigen receptor specificities demonstrated that allelic exclusion was imperfect. This led to concern that dual receptor lymphocytes pose a risk for autoimmunity - recognition of a foreign antigen through one receptor might activate a lymphocyte whose other antigen receptor is autoreactive. Indeed, dual receptor lymphocytes are enriched among autoreactive lymphocytes and can contribute to autoimmune disease pathogenesis in experimental settings. Dual T cell receptor (TCR) T cells are also enriched among alloreactive cells and contribute to graft-versus-host disease. On the other hand, dual receptor lymphocytes may broaden host protection against infection by increasing the number of antigen receptor specificities in the repertoire. The primary barrier to understanding the contribution of dual receptor lymphocytes in any of these immunological settings is simply that such cells are difficult to identify. For the case of B cells, it is now possible to identify dual immunoglobulin heavy chain-expressing cells (by exploiting natural allelic variants) and dual kappa light chain-expressing cells (via an engineered knockin of the human kappa constant region). Similar approaches to identify dual TCR T cells do not yet exist. Identification of dual T cell receptor T cells in mice is challenging due to the lack of allelic markers of the TCR? chain and because monoclonal antibodies exist for only ~16% of TCR V? segments. Estimating the number of dual TCR T cells in a population of lymphocytes has thus been accomplished by mathematical extrapolation rather than true quantification. The goal of the current project is to engineer a mouse that permits accurate identification, enumeration, and characterization of dual TCR?-expressing T cells in a normal polyclonal repertoire. Other investigators have successfully introduced epitope tags into the TCR? chain and TCR? chain in cell lines without disrupting the expression or function of the TCR. We propose here first to use a retroviral TCR expression system to identify an optimal site to insert an epitope tag in the mouse TCR? constant region. We will then engineer two gene targeted knockin mouse lines: one expressing a myc-tagged- and the other a FLAG-tagged-TCR? constant region. Crossing these mice will produce mice in which dual TCR?-expressing T cells can readily be identified based on their expression of both epitope tags. These mice will provide a powerful new approach to study dual TCR T cells in a wide range of immunological settings.
描述(由申请人提供):等位基因排斥确保大多数T和B淋巴细胞只表达一种抗原受体特异性-克隆选择理论的核心原则。在正常小鼠和人类中,一些T和B细胞表达两种不同的抗原受体特异性,这一发现表明等位基因排斥是不完美的。这引起了人们的担忧,即双重受体淋巴细胞对自身免疫构成了风险--通过一个受体识别外来抗原可能会激活另一个抗原受体具有自身反应的淋巴细胞。事实上,双受体淋巴细胞在自身反应性淋巴细胞中丰富,并在实验环境中有助于自身免疫性疾病的发病。双T细胞受体(TCR)T细胞也在同种异体反应细胞中丰富,并有助于移植物抗宿主病。另一方面,双受体淋巴细胞可以通过增加抗原受体特异性的数量来扩大宿主对感染的保护。理解双受体淋巴细胞在这些免疫学环境中的作用的主要障碍很简单,就是这种细胞很难识别。对于B的情况 细胞,现在可以鉴定双重免疫球蛋白重链表达细胞(通过利用天然的等位基因变体)和双重kappa轻链表达细胞(通过工程设计的 人类kappa恒定区的Knockin)。目前尚不存在识别双TCR T细胞的类似方法。在小鼠中鉴定双T细胞受体T细胞具有挑战性,因为 缺乏TCR的等位基因标记?因为只有16%的TCR V?细分市场。因此,估计淋巴细胞群体中双TCRT细胞的数量是通过数学外推而不是真正的量化来完成的。当前项目的目标是设计一种能够在正常的多克隆谱系中准确识别、计数和鉴定双TCR?表达的T细胞的小鼠。其他研究人员已经成功地将表位标签引入TCR?链条和TCR?在不破坏TCR的表达或功能的情况下,在细胞系中形成链。我们建议首先使用逆转录病毒TCR表达系统来确定在小鼠TCR中插入表位标签的最佳位置。恒定区域。然后我们将设计两个基因靶向敲击小鼠品系:一个表达带有myc标记的基因,另一个表达带有标志标记的TCR?恒定区域。将这些小鼠杂交将产生小鼠,在这些小鼠中,可以根据表达两个表位标签的T细胞很容易地识别出双重TCR?表达的T细胞。这些小鼠将为在广泛的免疫学环境中研究双TCR T细胞提供一种强大的新方法。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Bryce Binstadt其他文献

Bryce Binstadt的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Bryce Binstadt', 18)}}的其他基金

A novel autoinflammatory skin disease in a patient with mutations in alpha-T-catenin
α-T-连环蛋白突变患者的一种新型自身炎症性皮肤病
  • 批准号:
    10055124
  • 财政年份:
    2020
  • 资助金额:
    $ 7.6万
  • 项目类别:
A novel autoinflammatory skin disease in a patient with mutations in alpha-T-catenin
α-T-连环蛋白突变患者的一种新型自身炎症性皮肤病
  • 批准号:
    10197026
  • 财政年份:
    2020
  • 资助金额:
    $ 7.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    10624894
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    9815721
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Macrophages as effectors of autoimmune valvular carditis
巨噬细胞作为自身免疫性瓣膜性心脏病的效应器
  • 批准号:
    9086419
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Macrophages as effectors of autoimmune valvular carditis
巨噬细胞作为自身免疫性瓣膜性心脏病的效应器
  • 批准号:
    8754860
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    10418653
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Macrophages as effectors of autoimmune valvular carditis
巨噬细胞作为自身免疫性瓣膜性心脏病的效应器
  • 批准号:
    8890874
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
Pathogenesis of autoimmune valvular carditis
自身免疫性瓣膜性心脏病的发病机制
  • 批准号:
    9926159
  • 财政年份:
    2014
  • 资助金额:
    $ 7.6万
  • 项目类别:
A mouse to track dual TCR T cells
追踪双 TCR T 细胞的小鼠
  • 批准号:
    8660288
  • 财政年份:
    2013
  • 资助金额:
    $ 7.6万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 7.6万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了