Immunologic Studies in Ectothermin Vertebrates

描述(由申请人提供)：该项目的总体目标是更好地了解斑点叉尾鱼(Ictalurus Putatus)适应性和先天免疫反应的新的细胞和分子方面的新方面，斑点叉尾鱼是一种免疫学特征良好的硬骨鱼模型系统，具有相当重要的科学和经济意义。这项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，该基因座编码来自该基因座内不同基因的各种IGD亚型。将研究不同的IGD形式的结构、转录调节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B细胞的机制将从细胞中IgM和IGD亚型的表达方面进行研究。第二个目标集中在一个多样化的V区，其中包含一系列新的免疫类型受体(NITR)，这些受体在胞外结构域的数量以及细胞质激活或抑制基序的存在方面表现出结构多样性。有人建议研究硬骨NITR分子是否具有与人类白细胞受体复合体中编码的各种受体产物类似的功能。这些研究包括表达的评估、靶标识别和先天免疫反应的调节。这项拟议的工作有望提供关于这些潜在重要但知之甚少的分子在硬骨鱼免疫反应中扮演的功能角色的新信息。此外，这些分子可能被证明对理解适应性免疫和先天免疫功能进化分化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.