Interaction sites on H2Dd for Ly49A‐dependent natural killer (NK) cell licensing

NK cells become functionally competent through the interaction of NK cell inhibitory receptors with their cognate self‐MHC ligands, a process termed “licensing.” Licensed NK cells express self‐MHC‐specific receptors and can be triggered through their activation receptors to produce cytokines. Structural studies indicated that the Ly49A inhibitory receptor interacts with two sites on its H2Dd ligand. Site 2 encompasses the α1/α2/α3 domains of the H2Dd heavy chain and β2‐microglobulin (β2m), and is the functional binding site for the Ly49A in effector inhibition. However, it is currently unknown whether this same site is involved in Ly49A‐dependent licensing. Herein, we produced transgenic C57BL/6 mice expressing wild type, or mutant H2Dd molecules with site 1 or site 2 point mutations and studied whether Ly49A+ NK cells are licensed. Our data from these transgenic mice and human β2m‐transgenic, murine β2m‐deficient mice indicate that site 2 is critical in Ly49A‐dependent NK cell licensing. Thus, NK cell licensing through Ly49A involves interactions with its MHC ligand that are similar to those involved in effector inhibition.

Duke Scholars

Author Taewoong Choi Medicine, Hematologic Malignancies and Cellular Therapy