MHC Loci in the Control of Marek's Lymphoma

MHC 位点控制马立克氏淋巴瘤

基本信息

项目摘要

DESCRIPTION (provided by applicant): Oncogenic herpes viruses drive most cancers associated with HIV infection and other immunosuppressed conditions. The close association between immunity and tumor growth in these cancers is obvious. Relief of immunosuppression can bring cancer remission. Over time complex interactions have evolved between oncogenic virus, tumor and vertebrate host. The Marek's disease (MD) virus in the chicken provides useful model for learning more about the role of vertebrate genetics in controlling tumor growth caused by herpes virus transformation. Particular major histocompatibility complex (MHC) haplotypes in the chicken have strikingly strong roles in suppressing the growth of MD lymphomas, while other MHC haplotypes provide moderate or no protection. Two ostensibly identical recombinant MHC haplotypes were shown in earlier studies to differ in response to MD tumors. In preliminary work we have demonstrated that, although identical at class I, class II and a cluster of BG loci, the two recombinant haplotypes differ in crossover breakpoints within a restricted region in the vicinity of a distinctive BG locus that has intriguing features and is likely involved in signaling. In addition to the unusual BG locus there is a putative NK-cell receptor gene posited as important in controlling tumor growth (surrounded by long-inverted repeats that are typical of DNA predisposed to instability and increased homologous recombination in adjacent regions). We seek to 1) confirm the difference between the two recombinant haplotypes, BR2 and BR4 in response to challenge with MD virus and extend the test to include a third closely related recombinant haplotype BR3 using fully congenic strains now available in additional MDV challenge trials; 2) define the allelic differences at the candidate loci in BR2-BR4 recombinant haplotypes and haplotypes conferring high resistance and high susceptibility to MD tumors by resequencing the interval surrounding the crossover breakpoints; and 3) study the constitutive expression of candidate loci in organs associated with MDV infection and profile changes which occur in these and other loci during the course of viral infection and tumor formation in birds that bear the different MHC haplotypes and differ in tumor growth following infection.
描述(由申请人提供):致癌性疱疹病毒驱动大多数与HIV感染和其他免疫抑制条件相关的癌症。这些癌症中免疫力与肿瘤生长之间的密切关系是显而易见的。解除免疫抑制可以使癌症缓解。随着时间的推移,致癌病毒、肿瘤和脊椎动物宿主之间的复杂相互作用已经发展。鸡马立克氏病(MD)病毒为了解脊椎动物遗传学在控制疱疹病毒转化引起的肿瘤生长中的作用提供了有用的模型。特定的主要组织相容性复合体(MHC)单倍型在鸡有显着强大的作用,抑制MD淋巴瘤的生长,而其他MHC单倍型提供中度或无保护。两个表面上相同的重组MHC单倍型在早期的研究中显示出不同的MD肿瘤的反应。在初步工作中,我们已经证明,虽然在I类,II类和一个集群的BG基因座相同,两个重组单倍型不同的交叉断点内的一个独特的BG基因座,具有有趣的功能,并可能参与信号的附近的限制性区域。除了不寻常的BG基因座外,还有一个假定的NK细胞受体基因,该基因在控制肿瘤生长中起重要作用(被长反向重复序列包围,这是倾向于不稳定和相邻区域同源重组增加的DNA的典型特征)。我们寻求1)确认两种重组单倍型BR 2和BR 4在响应MD病毒攻击时的差异,并使用现在可用于额外MDV攻击试验的完全同源株将测试扩展到包括第三种密切相关的重组单倍型BR 3; 2)确定BR 2 - 3中候选基因座的等位基因差异,BR 4重组单倍型和通过重新测序交叉断点周围的间隔赋予对MD肿瘤的高抗性和高易感性的单倍型;和3)研究候选基因座在与MDV感染相关的器官中的组成型表达,以及在携带不同MDV的禽类中,在病毒感染和肿瘤形成过程中这些和其他基因座中发生的谱变化。MHC单倍型和不同的肿瘤生长感染后。

项目成果

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MARCIA M MILLER其他文献

MARCIA M MILLER的其他文献

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{{ truncateString('MARCIA M MILLER', 18)}}的其他基金

Equipment for Visualization of Fragile Subcellular Detail by Electron Microscopy
通过电子显微镜观察脆弱亚细胞细节的设备
  • 批准号:
    7595603
  • 财政年份:
    2009
  • 资助金额:
    $ 15.48万
  • 项目类别:
MHC Loci in the Control of Marek's Lymphoma
MHC 位点控制马立克氏淋巴瘤
  • 批准号:
    6909121
  • 财政年份:
    2004
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132030
  • 财政年份:
    1989
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132026
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132023
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132021
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132027
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132029
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
IMMUNOBIOLOGY OF THE MAJOR HISTOCOMPATIBILITY COMPLEX
主要组织相容性复合体的免疫生物学
  • 批准号:
    3132028
  • 财政年份:
    1985
  • 资助金额:
    $ 15.48万
  • 项目类别:
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