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通道鲶鱼（Ictalurus puntatus）的适应性和先天免疫反应的新细胞和分子方面，这是一种具有相当科学和经济重要性的免疫学特征的硬骨鱼模型系统。提出的研究的第一个目的是了解硬骨鱼IgH基因座的复杂遗传组织，该基因座编码来自不同基因的各种IgD同型。我们将研究不同形式的IgD的结构、转录调控以及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细胞的机制将通过IgM和IgD同种型的细胞表达进行研究。第二个目标侧重于包含新型免疫型受体（NITR）家族的多样化V区，这些受体在细胞外结构域的数量和细胞质激活或抑制基元的存在方面表现出结构多样性。研究建议调查硬骨鱼NITR分子是否具有类似于人类白细胞受体复合体内编码的各种受体产物的功能。这些研究包括评估表达、目标识别和先天免疫反应的调节。所提出的工作有望产生关于这些潜在的重要功能角色的新信息，但知之甚少，分子在硬骨鱼免疫反应中发挥作用。此外，这些分子可能对理解适应性和先天免疫功能进化差异的更基本方面很重要。

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.