Direct assessment of MHC class I binding by seven Ly49 inhibitory NK cell receptors

Mouse NK cells express at least seven inhibitory Ly49 receptors. Here we em ploy a semiquantitative cell-cell adhesion assay as well as class I/peptide tetramers to provide a comprehensive analysis of specificities of Ly49 rec eptors for class I MHC molecules in eight MHC haplotypes. Different Ly49 re ceptors exhibited diverse binding properties. The degree of class I binding was related to the extent of functional inhibition. The tetramer studies d emonstrated that neither glycosylation nor coreceptors were necessary for c lass I binding to Ly49 receptors and uncovered peptide-specific recognition by a Ly49 receptor. The results provide a foundation for interpreting and integrating many existing functional studies as well as for designing tests of NK cell development and self-tolerance.