NK cell recognition of MHC class I. NK cells are sensitive to peptide-binding groove and surface alpha-helical mutations that affect T cells.
NK cells directly or indirectly recognize MHC class I molecules, but the exact structures recognized remain poorly defined. We address the hypothesis that NK cells, like T cells, directly contact peptide/MHC class I complexes. This hypothesis predicts that NK-mediated killing is inhibited by amino acid substitutions in the MHC class I peptide-binding groove and in solvent-accessible alpha-helical residues proposed to contact the TCR. In our model system, target cell HLA-B*0702 inhibited killing by unstimulated peripheral blood NK cells. NK-mediated killing was increased significantly by 6 of 11 peptide-binding groove mutations and 6 of 12 TCR contact site mutations, but only 1 of 6 mutations outside these sites. Many of the mutations that inhibited NK-mediated killing prohibited killing by 12 alloreactive CTL clones. These data suggest that NK receptors directly contact HLA-B*0702, focusing on the peptide-binding groove and surrounding alpha-helices. NK cell lines exhibited multiple HLA recognition patterns, which is consistent with nonuniform expression of MHC receptors by NK cells. We propose that NK cells, like alpha beta T cells and some anti-MHC Abs, directly or indirectly recognize MHC-bound peptides.
Kurago
Z B
ZB
Department of Pathology, University of Iowa, Iowa City 52242.
Smith
K D
KD
Lutz
C T
CT
D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D015235:HLA-B Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D016297:Mutagenesis, Site-Directed / Q000276:immunology; D010455:Peptides / Q000276:immunology; D017433:Protein Structure, Secondary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000235:genetics
D015235:HLA-B Antigens; D010455:Peptides