Naper C, Rolstad B, Wonigeit K, Butcher G W, Vaage J T
Department of Anatomy, University of Oslo, Norway.
Int Immunol. 1996 Nov;8(11):1779-85. doi: 10.1093/intimm/8.11.1779.
We have previously presented evidence suggesting that the non-classical class I region of the rat MHC, RT1.C, encodes polymorphic molecules which induce the cytolytic activity of alloreactive NK cells. Those studies used target cells from a panel of MHC congenic rat strains possessing recombined portions of the RT1a, RT1l and RT1u MHC haplotypes. We have now examined in addition a set of rat strains bearing MHC haplotypes recombinant between RT1av1 and RT1c, and a more complex picture of the MHC control of rat NK alloreactivity has emerged. The expression of a major NK allodeterminant [the allogeneic lymphocyte cytotoxicity (ALC) determinant 2 or ALC-2, defined operationally using cold-target inhibition assays], appears to be under the control of both the RT1.C and the classical class I RT1.A region. Similarly, the alloreactive repertoires of NK cells from these recombinant strains are influenced by elements encoded within these two MHC class I regions. We present a model in which the classical class I autoantigen RT1.Ac exhibits dominant inhibition of NK cytotoxicity specific for the stimulatory determinant ALC-2 shared by the nonclassical class I molecules RT1.Cav1, RT1.Ca and RT1.Cc, and also prevents the deletion of NK cells of this specificity during their development.
我们之前已经提供了证据，表明大鼠主要组织相容性复合体（MHC）的非经典I类区域RT1.C编码多态性分子，这些分子可诱导同种异体反应性自然杀伤（NK）细胞的细胞溶解活性。那些研究使用了来自一组MHC同基因大鼠品系的靶细胞，这些品系拥有RT1a、RT1l和RT1u MHC单倍型的重组部分。我们现在还研究了一组携带RT1av1和RT1c之间重组MHC单倍型的大鼠品系，并且出现了关于大鼠NK同种异体反应性的MHC控制的更复杂情况。一种主要的NK同种异体决定簇[同种异体淋巴细胞细胞毒性（ALC）决定簇2或ALC - 2，通过冷靶抑制试验进行操作性定义]的表达似乎受RT1.C和经典I类区域RT1.A的控制。同样，来自这些重组品系的NK细胞的同种异体反应库也受到这两个MHC I类区域内编码元件的影响。我们提出了一个模型，其中经典I类自身抗原RT1.Ac对NK细胞毒性表现出显性抑制，这种毒性针对非经典I类分子RT1.Cav1、RT1.Ca和RT1.Cc共有的刺激决定簇ALC - 2，并且还防止这种特异性的NK细胞在其发育过程中被清除。
