Premium
Interaction sites on H2D d for Ly49A‐dependent natural killer (NK) cell licensing
Author(s) -
Choi Taewoong,
PoursineLaurent Jennifer,
Matsumoto Naoki,
Yokoyama Wayne M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.672.37
Subject(s) - receptor , microbiology and biotechnology , mhc class i , immunological synapse , chemistry , effector , major histocompatibility complex , natural killer cell , mutant , biology , t cell receptor , t cell , cytotoxic t cell , immune system , immunology , biochemistry , in vitro , gene
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 H2D d ligand. Site 2 encompasses the α1/α2/α3 domains of the H2D d heavy chain and β 2 ‐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 H2D d 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. Supported by the Howard Hughes Medical Institute and grants from the NIH.