HLA-B-ASTERISK-3501 - PEPTIDE INTERACTIONS - ROLE OF ANCHOR RESIDUES OF PEPTIDES IN THEIR BINDING TO HLA-B-ASTERISK-3501 MOLECULES

Two HLA-B3501 binding self-peptides, LPFDFTPGY (37F) and LPGPKFLQY (2 8H), were isolated from HLA-B3501 molecules expressed by cultured hum an B lymphoid cells. Both sequences were consistent with previously re ported motifs of HLA-B3501 binding peptides which carry proline at po sition 2 and tyrosine at position 9 as anchor residues. Direct binding of these peptides to HLA-B3501 molecules was quantitated by flow cyt ometry analysis of RMA-S cells transfected with the HLA-83501 gene (R MA-S-B3501). Both 37F and 28H peptides bound effectively to HLA-B*350 1 molecules. Substitution of amino acids at position 2 and/or 9 of HLA -B3501 binding peptides markedly reduced their binding to HLA-B*3501 molecules. These results indicate that two anchor residues, proline at position 2 and tyrosine at position 9 are critical in binding of pept ides to HLA-B3501 molecules. Insertion of up to four glycine residues at position 8 of the peptide 37F did not affect its binding affinity to HLA-B3501 molecules. These results indicate that long peptides can effectively bind to HLA class I molecules provided that anchor residu es are conserved.