Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity.
Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed on subsets of natural killer (NK) cells and T cells, for which no endogenous ligands are known. Here, we show that KLRG1 binds three of the classical cadherins (E-, N-, and R-), which are ubiquitously expressed in vertebrates and mediate cell-cell adhesion by homotypic or heterotypic interactions. By expression cloning using the mouse KLRG1 tetramer as a probe, we identified human E-cadherin as a xenogeneic ligand. We also identified a syngeneic interaction between mouse KLRG1 and mouse E-cadherin. Furthermore, we show that KLRG1 binds N- and R-cadherins. Finally, we demonstrate that E-cadherin binding of KLRG1 prevents the lysis of E-cadherin-expressing targets by KLRG1+ NK cells. These results suggest that KLRG1 ligation by E-, N-, or R-cadherins may regulate the cytotoxicity of killer cells to prevent damage to tissues expressing the cadherins.
Ito
Masayuki
M
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-8562 Chiba, Japan.
Maruyama
Takuma
T
Saito
Naotoshi
N
Koganei
Satoru
S
Yamamoto
Kazuo
K
Matsumoto
Naoki
N
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology
D015820:Cadherins; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; C083970:R-cadherin; D011971:Receptors, Immunologic