Implications of HLA-E allele expression and different HLA-E ligand diversity for the regulation of NK cells.
The interaction of HLA-E with CD94/NKG2A is dependant on the binding of HLA class I signal sequence derived peptides to HLA-E. In the caucasoid population two HLA-E alleles are observed at equal frequencies. Here we study the functional differences between the two HLA-E molecules with regard to cell surface expression, peptide binding, and potential to inhibit lytic activity of a CD94/NKG2A(+) NK cell line. In contrast to the HLA-E(R) allele, the HLA-E(G) allele shows considerable cell surface expression even in the absence of endogenous HLA class I signal sequence derived HLA-E ligands. Eighteen HLA-E allele/HLA-E ligand combinations were analyzed. No correlation between cell surface expression of HLA-E and NK cell inhibition was observed. The peptides present in the signal sequences of HLA-B15, -Cw0402, and -Cw7 bound to both HLA-E alleles but did not lead to an inhibition of NK cell lysis. In our experimental system the peptides A2 and G were not effective with regard to NK cell inhibition when bound to the HLA-E(R) allele. These results may be of functional significance particularly in the placenta where the only HLA-E ligands are derived from HLA-G and -C.
Maier
S
S
Institut für Anthropologie und Humangenetik, Ludwig-Maximilians-Universität, Munich, Germany.
Grzeschik
M
M
Weiss
E H
EH
Ulbrecht
M
M
D000483:Alleles; D015703:Antigens, CD / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009842:Oligopeptides / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D014162:Transfection; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009842:Oligopeptides; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human