ROLE OF THE MHC IN EARLY MAMMALIAN DEVELOPMENT

主要组织相容性复合体(MHC)在早期哺乳动物中的作用 将对发展情况进行调查。植入前的一个关键因素 胚胎发育是早期卵裂分裂的时机。我们 最近发现了一种基因，Ped(植入前胚胎发育)， 与H-2复合体有关，这影响了第一次 卵裂分裂和随后的小鼠胚胎发育率。 对同源菌株的分析表明，某些单倍型的胚胎 (K和r)的胚胎发育速度较慢，而其他 单倍型(b、d、q、a、S、u)发展较快。进一步的遗传分析 提出了Ped基因表达的新方法。第一，与H-2相关的链接 PED基因对H-2复合体的检测将通过回交分析进行 胚胎。接下来，将确定Ped基因是否会影响时间 植入的或妊娠的长度。这些数据很重要，因为 人类体内可能存在与人类白细胞抗原复合体相关的Ped基因 影响人类发展的时间。的另一个重要方面 早期胚胎发育是细胞表面的结构和功能 在胚胎上发现的蛋白质。一类细胞表面分子H-2 抗原，已被证明对各种 成体细胞之间的细胞间相互作用。然而，H-2的检测 小鼠早期胚胎上的抗原一直是困难和有争议的。 使用我们开发的一种高度敏感的细胞毒性技术 实验室，我们已经能够证明H-2抗原存在于 K、b和d单倍型的胚胎。进一步分析不同类型之间的关系 提出了在小鼠胚胎上表达H-2抗原。两者都是传统的 将使用抗血清和单抗，阳性结果将 用纯化的H-2抗原进行阻断研究证实了这一点。最后， 关于小鼠胚胎上的H-2抗原是否具有生物学意义的问题 将通过尝试杀死小鼠胚胎来探索功能 细胞毒性T淋巴细胞(CTL)。因为CTL必须识别H-2抗原 为了杀死他们的目标，CTL杀死胚胎将是 小鼠胚胎上的H-2抗原不仅是 在血清学上可以检测到，但在生物学上也是有效的。

The role of the major histocompatibility complex (MHC) in early mammalian development will be investigated. A key factor in preimplantation embryonic development is the timing of the early cleavage divisions. We have recently discovered a gene, Ped (Preimplantation embryo development), associated with the H-2 complex, which influences the time of the first cleavage division and the subsequent rate of mouse embryonic development. Analysis of congenic strains has shown that embryos of certain haplotypes (k and r) exhibit a slow rate of development, whereas embryos of other haplotypes (b,d,q,a,s,u) develop at a fast rate. Further genetic analysis of Ped gene expression is proposed. First, linkage of the H-2 associated Ped gene to the H-2 complex will be tested by analysis of backcross embryos. Next, it will be determined whether the Ped gene affects the time of implantation or length of gestation. These data are important because there may be Ped genes in humans, associated with the HLA complex, that influence the timing of human development. Another important aspect of early embryonic development is the structure and function of cell surface proteins found on embryos. One class of cell surface molecules, the H-2 antigens, have been shown to be crucially important to a variety of cell-cell interactions between adult cells. However, the detection of H-2 antigens on early mouse embryos has been difficult and controversial. Using a highly sensitive cytotoxicity technique developed in our laboratory, we have been able to show the presence of H-2 antigens on embryos of the k, b, and d haplotypes. Further analysis of the types of H-2 antigens expressed on mouse embryos is proposed. Both conventional antisera and monoclonal antibodies will be used, and positive results will be confirmed by blocking studies with purified H-2 antigens. Finally, the question of whether H-2 antigens on mouse embryos are biologically functional will be probed by attempting to kill mouse embryos with cytotoxic T lymphocytes (CTL's). Since CTL's must recognize H-2 antigens in order to kill their targets, killing of the embryos by CTL's will be excellent evidence that H-2 antigens on mouse embryos are not only serologically detectable, but biologically functional, as well.