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.