Sundbäck Jonas, Achour Adnane, Michaëlsson Jakob, Lindström Hannah, Kärre Klas
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
J Immunol. 2002 Jan 15;168(2):793-800. doi: 10.4049/jimmunol.168.2.793.
Mouse NK cells express Ly-49 receptors specific for classical MHC class I molecules. Several of the Ly-49 receptors have been characterized in terms of function and ligand specificity. However, the only Ly-49 receptor-ligand interaction previously described in detail is that between Ly-49A and H-2D(d), as studied by point mutations in the ligand and the crystal structure of the co-complex of these molecules. It is not known whether other Ly-49 receptors bind MHC class I in a similar manner as Ly-49A. Here we have studied the effect of mutations in Ly-49C on binding to the MHC class I molecules H-2K(b), H-2D(b), and H-2D(d). The MHC class I molecules were used as soluble tetramers to stain transiently transfected 293T cells expressing the mutated Ly-49C receptors. Three of nine mutations in Ly-49C led to loss of MHC class I binding. The three Ly-49C mutations that affected MHC binding correspond to Ly-49A residues that are in contact or close to H-2D(d) in the co-crystal, demonstrating that MHC class I binding by Ly-49C is dependent on residues in the same area as that used by Ly-49A for ligand contacts.
小鼠自然杀伤（NK）细胞表达对经典MHC I类分子具有特异性的Ly-49受体。其中一些Ly-49受体已在功能和配体特异性方面得到了表征。然而，之前详细描述的唯一Ly-49受体-配体相互作用是Ly-49A与H-2D(d)之间的相互作用，这是通过对配体进行点突变以及对这些分子的共复合物晶体结构进行研究得出的。尚不清楚其他Ly-49受体是否以与Ly-49A类似的方式结合MHC I类分子。在此，我们研究了Ly-49C中的突变对其与MHC I类分子H-2K(b)、H-2D(b)和H-2D(d)结合的影响。将MHC I类分子用作可溶性四聚体，以对瞬时转染表达突变Ly-49C受体的293T细胞进行染色。Ly-49C的九个突变中有三个导致MHC I类分子结合丧失。影响MHC结合的这三个Ly-49C突变对应于在共晶体中与H-2D(d)接触或接近的Ly-49A残基，表明Ly-49C对MHC I类分子的结合依赖于与Ly-49A用于配体接触的相同区域中的残基。
