HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A.
We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.
Lee
N
N
The Clinical Research Division, Fred Hutchinson Cancer Research Center, 1124 Columbia St., M374, Seattle, WA 98104-2092, USA.
Llano
M
M
Carretero
M
M
Ishitani
A
A
Navarro
F
F
López-Botet
M
M
Geraghty
D E
DE
D015703:Antigens, CD / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D019281:Dimerization; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism*; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D011971:Receptors, Immunologic; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human