A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

描述（由申请人提供）：非洲爪蟾长期以来一直被成功地用作研究复杂免疫系统发育的选择的变温脊椎动物物种。此外，X.非洲爪蟾免疫系统的发育发生在两个不同的时期：一次是在幼虫期，另一次是在从有免疫活性的幼虫到有免疫活性的成虫的变态过渡期。由于幼虫形式是自由游动的，并且适合于各种手术和非手术干预，因此可以获得不可能从哺乳动物的子宫内研究中获得的有价值的信息（例如，对成人特异性抗原的自身耐受性的发展，第二T细胞库的获得，以及自然环境中T细胞亚群的个体发生）。 此外，变态是神经驱动的，这允许在发育中的免疫系统中检查免疫相关的神经内分泌-免疫系统相互作用。非洲爪蟾免疫学的另一个关键方面，使其重要的模型是有据可查的缺乏经典和非经典的MHC I类表达在前变态幼虫期。最后，表达或缺乏MHC I类和II类分子的可移植肿瘤细胞系也有助于使用非洲爪蟾作为天然存在的“敲除”物种。该提案的广泛目标是通过以下方式进一步发展非洲爪蟾作为非哺乳动物免疫生物学重点模型：（1）确保非洲爪蟾的不同克隆、品系和物种的系统繁殖和饲养;（2）组织信息和现有研究材料的中央储存库（例如，细胞系、DNA文库、mAb、动物）;和（3）产生用于免疫学研究的新工具（例如，新的单克隆抗体、cDNA文库、细胞系、转基因青蛙）。许多现有的和新的研究领域应该从满足这些目标中受益。展望：X.平滑为：一种非哺乳动物模型，用于研究：（1）肿瘤免疫;（2）个体发育过程中的自身耐受和自身免疫;（3）宿主-病原体相互作用;（4）基因组进化和基因组调控;（5）免疫毒理学（6）热休克蛋白在免疫中的作用;（7）非经典MHC I类抗原的功能;（8）Toll样受体在免疫中的进化（结构和功能）。

DESCRIPTION (provided by applicant): Xenopus laevis has long been used successfully as the ectothermic vertebrate species of choice for studying the phylogeny of the complex immune system. In addition, X. laevis has proved to be an excellent model system for answering fundamental immunological questions that are not phylogenetically restricted to a given taxon. In part, this is because development of the Xenopus immune system occurs at two distinct times: once during larval life, and then again during the metamorphic transition from immunocompetent larva to immunocompetent adult. Since the larval form is free-swimming and amenable to a variety of surgical and nonsurgical interventions, valuable information can be obtained that is not possible to obtain from in utero studies of mammals (e.g., development of self-tolerance to adult specific antigens, acquisition of a second T-cell repertoire, and ontogeny of T-cell subsets in a natural setting). Moreover, metamorphosis is hormonally driven which permits examination of immunologically relevant neuroendocrine-immune system interactions in a developing immune system. Another critical aspect of Xenopus immunology that makes it important as a model is the well-documented absence of classical and non-classical MHC class I expression during the pre-metamophic larval period. Finally, transplantable tumor cell lines that either express or lack MHC class I and II molecules also contribute to the use of Xenopus as a naturally-occurring "knockout" species. The broad objectives of this proposal are to further develop Xenopus laevis as a non-mammalian immunobiologically-focused model by: (1) assuring the systematic breeding and husbandry of different clones, strains, and species of Xenopus; (2) organizing a central repository of information and existing research materials (e.g., cell lines, DNA libraries, mAbs, animals) readily available to the scientific community; and (3) generating new tools for immunological research (e.g., new mAbs, cDNA libraries, cells lines, transgenics frogs). Many areas of existing and new research should benefit from satisfying these aims. We envision: further development of X. laevis as: a nonmammalian model for studying: (1) tumor immunity; (2) self-tolerance and autoimmunity during ontogeny; (3) host-pathogen interactions; (4) genome evolution and genomic regulation; (5) immunotoxicology (e.g. endocrine disruptors); (6) the role of heat shock proteins in immunity; (7) the function of nonclassical MHC class I antigens; and (8) the evolution of toll-like receptors (structure and function) in immunity.