A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY

描述（由申请人提供）：非洲爪蟾（Xenopus laevis）长期以来一直被成功地用作研究复杂免疫系统系统发育的恒温脊椎动物。此外，狐猴已被证明是一个很好的模型系统，可以回答不受系统发育限制的基本免疫学问题。在某种程度上，这是因为爪蟾免疫系统的发育发生在两个不同的时期：一次是在幼虫时期，然后是在从具有免疫能力的幼虫到具有免疫能力的成虫的蜕变过程中。由于幼虫形态是自由游动的，可以接受各种手术和非手术干预，因此可以获得从哺乳动物的子宫研究中无法获得的有价值的信息（例如，对成人特异性抗原的自我耐受性的发展，第二t细胞库的获得，以及t细胞亚群在自然环境中的个体发生）。

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.