| First Author | Choi T | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 7 | Pages | 3911-7 |
| PubMed ID | 21335486 | Mgi Jnum | J:170469 |
| Mgi Id | MGI:4946549 | Doi | 10.4049/jimmunol.1004168 |
| Citation | Choi T, et al. (2011) Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands. J Immunol 186(7):3911-7 |
| abstractText | NK cells become functionally competent to be triggered by their activation receptors through the interaction of NK cell inhibitory receptors with their cognate self-MHC ligands, an MHC-dependent educational process termed 'licensing.' For example, Ly49A(+) NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2D(d), whereas Ly49C(+) NK cells are licensed by H2K(b). Structural studies indicate that the Ly49A inhibitory receptor may interact with two sites, termed site 1 and site 2, on its H2D(d) ligand. Site 2 encompasses the alpha1/alpha2/alpha3 domains of the H2D(d) H chain and beta(2)-microglobulin (beta2m) and is the functional binding site for Ly49A in effector inhibition. Ly49C functionally interacts with a similar site in H2K(b). However, it is currently unknown whether this same site is involved in Ly49A- or Ly49C-dependent licensing. In this study, we produced transgenic C57BL/6 mice expressing wild-type or site 2 mutant H2D(d) molecules and studied whether Ly49A(+) NK cells are licensed. We also investigated Ly49A- and Ly49C-dependent NK licensing in murine beta2m-deficient mice that are transgenic for human beta2m, which has species-specific amino acid substitutions in beta2m. Our data from these transgenic mice indicate that site 2 on self-MHC is critical for Ly49A- and Ly49C-dependent NK cell licensing. Thus, NK cell licensing through Ly49 involves specific interactions with its MHC ligand that are similar to those involved in effector inhibition. |
