Department of Medicine, McMaster University Rm 3V39, Hamilton, ON, Canada.
Am J Reprod Immunol. 2010 Feb;63(2):93-103. doi: 10.1111/j.1600-0897.2009.00774.x. Epub 2009 Dec 20.
Allogeneic pregnancies have a survival advantage over syngeneic pregnancies, and paternal Class I MHC antigens have been implicated. In humans, HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described. However, the mechanism of prevention of embryo demise in utero has not been critically assessed, and a number of conflicting ideas have not been addressed. The alphabeta T-cell receptor recognizes peptide bound to the groove in Class I MHC, and peptides have profound effects on the interaction of KIR receptors on T and NK cells with Class I MHC.
Data on prevention of pregnancy loss (abortion) in poly IC-treated mice were reviewed along with information about prevention of losses in the abortion-prone CBA x DBA/2 model. This information was combined with data on paternal antigen expression at different times in pregnancy when key events determining outcome are thought to transpire, and role of tolerance signaling molecules such as CD200. Current data on models supporting a role for 'true' uterine NK cells (TuNKs) versus blood NK cells in the uterus (BuNKs) and role of MHC-KIR interaction were reviewed along with incompatible data in the literature.
Whilst paternal Class I MHC appears important, there is an important role for paternal non-MHC minor antigens (small peptides) that bind to the antigen-presenting groove of Class I MHC. BuNKs along with CD8(+) T cells and Treg cells appear more important than TuNKs where the role of the latter appears primarily to promote angiogenesis. When during pregnancy the maternal immune system cells are first exposed to paternal Class I + peptide is uncertain, but at the time of implantation, if not earlier, seems likely.
Suppression of pregnancy loss by paternal/embryo Class I MHC depends on the presence of paternal peptides. This greatly complicates existing models of Class I-KIR interactions in feto-maternal tolerance or rejection. It is important to consider all the data when devising explanatory models.
同种异体妊娠比同基因妊娠有生存优势，并且已经涉及到父系Ⅰ类 MHC 抗原。在人类中，HLA-C 和 HLA-G 和 E 由胎儿滋养层的亚群表达。在小鼠中，已描述了 Qa-2，一种Ⅰ类抗原，和经典 H-2K 抗原。然而，尚未对预防宫内胚胎死亡的机制进行严格评估，并且一些相互矛盾的想法尚未得到解决。αβ T 细胞受体识别与Ⅰ类 MHC 凹槽结合的肽，并且肽对 KIR 受体与 T 和 NK 细胞与Ⅰ类 MHC 的相互作用有深远的影响。
回顾了聚肌苷酸处理的小鼠中预防妊娠丢失（流产）的数据，以及易发生流产的 CBA x DBA/2 模型中预防丢失的信息。将这些信息与妊娠不同时间父系抗原表达的信息结合起来，这些时间被认为是决定结果的关键事件发生的时间，以及与耐受信号分子（如 CD200）的作用结合起来。同时还回顾了支持“真正的”子宫自然杀伤细胞（TuNKs）与血液自然杀伤细胞（BuNKs）在子宫中的作用以及 MHC-KIR 相互作用的模型中的当前数据，以及文献中的不兼容数据。
虽然父系Ⅰ类 MHC 似乎很重要，但父系非 MHC 次要抗原（小肽）与Ⅰ类 MHC 的抗原呈递凹槽结合也具有重要作用。BuNKs 与 CD8(+) T 细胞和 Treg 细胞一样重要，而 TuNKs 的作用似乎主要是促进血管生成。母体免疫系统细胞首次接触父系Ⅰ类+肽的时间尚不确定，但在植入时似乎是这样，或者更早。
父系/胚胎Ⅰ类 MHC 对妊娠丢失的抑制取决于父系肽的存在。这极大地复杂化了现有的 feto-maternal 耐受或排斥中Ⅰ类-KIR 相互作用的模型。在设计解释模型时，考虑所有数据非常重要。
