Peptide sequence requirements for the recognition of HLA-B*2705 by specific natural killer cells.
NK clones that were inhibited by target cell expression of HLA-B*2705 displayed peptide-specific recognition of HLA-B*2705. To evaluate the specificity of this recognition, synthetic versions of 14 endogenous ligands of HLA-B*2705 were tested for their ability to provide protection from NK-mediated lysis by binding to surface HLA-B*2705 molecules on RMA-S cells deficient in the transporter for Ag presentation. Several unrelated peptides inhibited lysis by the same NK clones. Despite similar capacities to stabilize HLA-B*2705 molecules on RMA-S cells, the 14 peptides differed widely in their abilities to provide protection. Single amino acid substitutions in both a protective and a nonprotective peptide revealed the importance of residues 7 and 8 in the peptide for recognition by NK clones, thus localizing the peptide influence to a polymorphic region of the alpha-helix of HLA class I molecules known to control discrimination among allelic variants of HLA-B and HLA-C by NK cells.
Peruzzi
M
M
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Parker
K C
KC
Long
E O
EO
Malnati
M S
MS
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D015235:HLA-B Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015235:HLA-B Antigens; D008024:Ligands; D009842:Oligopeptides; C073119:TAP1 protein, human