Recognition of H-2K(b) by Ly49Q suggests a role for class Ia MHC regulation of plasmacytoid dendritic cell function.
Ly49Q is a member of the polymorphic Ly49 family of NK cell receptors that displays both a high degree of conservation and a unique expression pattern restricted to myeloid lineage cells, including plasmacytoid dendritic cells (pDC). The function and ligand specificity of Ly49Q are unknown. Here, we use reporter cell analysis to demonstrate that a high-affinity ligand for Ly49Q is present on H-2(b), but not H-2(d), H-2(k), H-2(q), or H-2(a)-derived tumor cells and normal cells ex vivo. The ligand is peptide-dependent and MHC Ia-like, as revealed by its functional absence on cells deficient in TAP-1, beta(2)m, or H-2K(b)D(b) expression. Furthermore, Ly49Q is specific for H-2K(b), as the receptor binds peptide-loaded H-2K(b) but not H-2D(b) complexes, and Ly49Q recognition can be blocked using anti-K(b) but not anti-D(b) mAb. Greater soluble H-2K(b) binding to ligand-deficient pDC also suggests cis interactions of Ly49Q and H-2K(b). These results demonstrate that Ly49Q efficiently binds H-2K(b) ligand, and suggest that pDC function, like that of NK cells, is regulated by classical MHC Ia molecules. MHC recognition capability by pDC has important implications for the role of this cell type during innate immune responses.
Tai
Lee-Hwa
LH
Institut de Recherches Cliniques de Montréal (IRCM), Laboratory of Molecular Immunology, Université de Montréal, Montréal, Quebec, Canada.
Goulet
Marie-Line
ML
Belanger
Simon
S
Troke
Angela D
AD
St-Laurent
Aaron G
AG
Mesci
Aruz
A
Toyama-Sorimachi
Noriko
N
Carlyle
James R
JR
Makrigiannis
Andrew P
AP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000950:Antigens, Ly / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000276:immunology*; D008024:Ligands; D051379:Mice; D055650:NK Cell Lectin-Like Receptor Subfamily A; D009369:Neoplasms / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D055630:Receptors, NK Cell Lectin-Like
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C527089:Klra17 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like