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The Self-Nonself Discrimination System of Vertebrates : Structure, Function, and Origin

脊椎动物的自我-非自我辨别系统：结构、功能和起源

基本信息

批准号：
09044247
负责人：
KASAHARA Masanori
金额：
$ 2.43万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至无数据
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09044247/
关键词：
Major histocompatibility complex Evolution Self-nonself discrimination system Chromosome duplication

项目摘要

The exquisite self-nonself discrimination system, as we see now in man and mouse, was built over evolutionary time. Therefore, to truly understand the biological significance of the system, it is insufficient to study only humans and mice. The aim of the present work was, thus, to study the structure, function, and origin of the vertebrate self-nonself discrimination system employing a wide variety of animals ranging from mammals to fish. The head investigator found that the genome of mammals such as humans and mice contains the regions paralogous to the major histocompatibility complex (MHC). These regions and the MHC region appear to have diverged as a result of chromosomal duplication involving the ancestors of the antigen processing genes such as LMP (low molecular mass polypeptide) and TAP (transporter associated with antigen processing). Phylogenetic analysis showed that the chromosomal duplications probably took place early in vertebrate evolution, in a common ancestor of jawed vertebrates. Dr.Flajnik found that the LMP and TAP genes are located more closely to MHC class I than to class II genes in the amphibian Xenopus laevis. This is in contrast to the fact that these genes reside in the class II region of the mammalian MHC,and suggests that the Xenopus type gene organization is a primordial one. Dr.Du Pasquier found that the Xenopus CIX gene coding for the Ig superfamily member expressed specifically in cortical thymocytes is linked to the MHC.Dr.Kaufman established a cosmid contig map covering the entire chicken MHC.

正如我们现在在人类和老鼠身上看到的那样，精致的自我-非自我辨别系统是在进化过程中建立起来的。因此，要真正理解该系统的生物学意义，仅研究人类和小鼠是不够的。因此，本工作的目的是研究脊椎动物自我-非自我辨别系统的结构、功能和起源，该系统采用了从哺乳动物到鱼类的各种动物。首席研究员发现，人类和小鼠等哺乳动物的基因组包含与主要组织相容性复合体（MHC）同源的区域。这些区域和MHC区域似乎由于涉及抗原加工基因如LMP（低分子量多肽）和TAP（与抗原加工相关的转运蛋白）的祖先的染色体复制而分化。系统发育分析表明，染色体复制可能发生在脊椎动物进化的早期，在有颌脊椎动物的共同祖先。弗拉伊尼克博士发现，在两栖动物非洲爪蟾中，LMP和TAP基因更接近MHC I类，而不是II类基因。这与这些基因位于哺乳动物MHC的II类区域的事实相反，并表明爪蟾型基因组织是原始的。杜帕斯基耶博士发现，编码在皮质胸腺细胞中特异表达的IG超家族成员的非洲爪蟾CIX基因与MHC相连，考夫曼博士建立了覆盖整个鸡MHC的粘粒重叠群图谱。