Probing the Interactions of NK Cell Receptors with Ligand Expressed in trans and cis

Certain receptors on natural killer (NK) cells, which are specific for MHC class I (MHC-I) molecules, do not only interact with ligand expressed on opposing cell membranes (in trans ) but also interact with those on the same cell membrane (in cis ). Cis interactions have been demonstrated for only a small number of cell surface receptors. However, this has not been tested systematically, raising the possibility that additional receptors may be able to bind ligand expressed in cis . Here we describe a number of approaches to evaluate trans and cis binding of the Ly49A NK cell receptor to its H-2D^d ligand. These procedures should facilitate the investigation of cis/trans interactions of other receptor–ligand pairs and simplify the analysis of NK cell receptor variants.