Immunologic Studies in Ectothermin Vertebrates

描述（由申请人提供）：本项目的总体目标是更好地了解新的细胞和分子方面的适应性和先天免疫反应的渠道鲶鱼（Ictalurus puntatus），免疫学良好的特点硬骨鱼模型系统的相当大的科学和经济的重要性。建议的研究的第一个目的是了解复杂的遗传组织的硬骨鱼IgH基因座，编码不同的基因内的基因的各种IgD同种型。不同的IgD形式将研究它们的结构，转录调控，并在硬骨鱼适应性免疫反应中的作用。此外，硫氧还蛋白激活硬骨鱼B细胞的机制将研究IgM和IgD同种型的细胞表达。第二个目标集中在一个多样化的V区含有家庭的新型免疫型受体（NITR），表现出结构多样性的胞外结构域的数量，和存在的细胞质激活或抑制基序。研究拟调查硬骨鱼NITR分子是否具有类似于人类白细胞受体复合物内编码的各种受体产物的功能。这些研究包括评估表达、靶标识别和先天免疫应答的调节。拟议的工作预计将产生新的信息，这些潜在的重要的功能作用，但知之甚少，分子在硬骨鱼免疫反应中发挥作用。此外，这些分子在理解适应性和先天免疫功能的进化分歧的更基本方面可能是重要的。

DESCRIPTION (provided by applicant): The overall objective of this project is to better understand novel cellular and molecular aspects of adaptive and innate immune responses in the channel catfish (Ictalurus puntatus), an immunologically well-characterized teleost model system of considerable scientific and economic importance. The first aim of the proposed studies deals with understanding the complex genetic organization of the teleost IgH locus, which encodes various IgD isotypes from different genes within the locus. The different IgD forms will be studied with respect to their structure, transcriptional regulation, and role in teleost adaptive immune responses. In addition, the mechanism by which thioredoxin activates teleost B cells will be investigated with regard to cellular expression of IgM and IgD isotypes. The second aim focuses on a diversified V region containing family of novel immune-type receptors (NITR) that exhibit structural diversity with respect to number of extracellular domains, and presence of cytoplasmic activating or inhibitory motifs. Studies are proposed to investigate whether or not teleost NITR molecules have functions analogous to the various receptor products encoded within the human leukocyte receptor complex. These studies include assessment of expression, target recognition, and regulation of innate immune responses. The proposed work is expected to yield novel information concerning the functional roles these potentially important, but poorly understood, molecules play in teleost immune responses. Furthermore, these molecules may prove important in understanding the more fundamental aspects of the evolutionary divergence of adaptive and innate immune functions.