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

正如我们现在在人类和老鼠身上看到的那样，这种精致的自我-非自我歧视系统是在进化过程中建立起来的。因此，要真正了解该系统的生物学意义，仅研究人类和老鼠是不够的。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，该系统使用了从哺乳动物到鱼类的各种动物。首席研究人员发现，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)平行的区域。这些区域和MHC区域似乎是由于涉及抗原处理基因的祖先的染色体复制的结果，例如LMP(低分子质量多肽)和TAP(与抗原处理相关的转运蛋白)。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，在有颌骨的脊椎动物的共同祖先中。Flajnik博士发现，在非洲爪哇两栖动物中，LMP和TAP基因与MHC I类基因的位置比与II类基因的位置更近。这与这些基因位于哺乳动物MHC的II类区域的事实相反，表明非洲爪哇类型的基因组织是原始的。Du Pasquier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Xenopus CIX基因与MHC相连。考夫曼博士建立了一个覆盖整个鸡MHC的粘粒重叠群图。

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.