Children's Research Institute, University of South Florida/All Children's Hospital, 140 Seventh Avenue South, St. Petersburg, Florida 33701.
Integr Comp Biol. 2003 Apr;43(2):331-7. doi: 10.1093/icb/43.2.331.
The prototypic forms of teleost novel immune-type receptors (NITRs) consist of a variable (V) region, a unique V-like C2 (V/C2) domain, a transmembrane region and a cytoplasmic tail containing immunoreceptor tyrosine-based inhibition motifs (ITIMs). NITRs encode diversified V regions in large multigene families but do not undergo somatic rearrangement. Studies in four different bony fish model systems have identified a number of different organizational forms of NITRs. Specifically, NITR genes encode N-terminal ectodomains of the V-type but otherwise vary in the: total number of extracellular immunoglobulin domains, number and location of joining (J) region-like motifs, presence of transmembrane regions, presence of charged residues within transmembrane regions, presence of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails. V region-containing NITRs constitute a far more complex family than recognized originally and currently include individual members that potentially function through inhibitory as well as activating mechanisms. The genomic organization of the NITR gene cluster as well as the structural diversity and overall architecture of the NITR proteins is reminiscent of genes encoded at the mammalian leukocyte receptor cluster (LRC); however, there presently is no functional evidence to support an orthologous relationship between NITR and LRC gene products. Comparisons of the predicted structures of the NITRs have identified several short regions of sequence identity and a novel cloning strategy has been devised that selects for secretory and transmembrane proteins that encode these short motifs. Using this approach, related genes termed immune-type receptors (ITRs) have been identified in cartilaginous fish. Taken together, these studies indicate that leukocyte regulatory receptors, including those that mediate natural killer function, might have emerged early in vertebrate evolution and that the NITR/ITR genes represent a new and potentially highly significant link between innate and adaptive immune responses.
原型形式的硬骨鱼新型免疫受体（NITRs）由一个可变区（V），一个独特的 V 样 C2（V/C2）域，一个跨膜区和一个含有免疫受体酪氨酸抑制基序（ITIMs）的细胞质尾部组成。NITRs 在大型多基因家族中编码多样化的 V 区，但不经历体细胞重排。在四个不同的硬骨鱼模型系统中的研究已经确定了许多不同的 NITR 组织形式。具体来说，NITR 基因编码 V 型的 N 端胞外结构域，但在以下方面存在差异：细胞外免疫球蛋白结构域的总数，连接（J）区样基序的数量和位置，跨膜区的存在，跨膜区中带电荷残基的存在，细胞质尾部的存在，以及/或细胞质尾部中 ITIM（s）的分布。含有 V 区的 NITRs 构成了一个远比最初认识到的更为复杂的家族，目前包括可能通过抑制和激活机制发挥作用的个体成员。NITR 基因簇的基因组组织以及 NITR 蛋白的结构多样性和整体结构与哺乳动物白细胞受体簇（LRC）编码的基因相似；然而，目前没有功能证据支持 NITR 和 LRC 基因产物之间的同源关系。对 NITRs 的预测结构的比较确定了几个短序列同一性区域，并设计了一种新的克隆策略，该策略选择编码这些短基序的分泌蛋白和跨膜蛋白。使用这种方法，在软骨鱼类中鉴定出了相关基因，称为免疫型受体（ITRs）。综上所述，这些研究表明白细胞调节受体，包括那些介导自然杀伤功能的受体，可能在脊椎动物进化的早期就出现了，而 NITR/ITR 基因代表了先天免疫和适应性免疫反应之间的一个新的、潜在的非常重要的联系。
