The HLA-B14 peptide binding site can accommodate peptides with different combinations of anchor residues.
Most peptides that bind to a particular major histocompatibility complex class I molecule share amino acid residues important for binding at one or two positions. Sequence analyses of peptides bound to HLA-B14 revealed at least four candidates for these so-called anchor residues: Arg at P2, Tyr at P3, Arg at P5, and Leu at P9. Combinations of any three of these amino acids sufficed for binding to HLA-B14 in vitro. Using this information, we identified an antigenic peptide critical for cytotoxic T lymphocyte recognition of virus-infected cells. Molecular models of HLA-B14 peptide complexes were constructed to investigate how the potential anchor residues might function. By using binding data to calculate the contribution to binding of each amino acid at anchor positions and predicting the stability of all possible nonapeptide complexes that could be formed from antigenic proteins, we estimate that three known antigenic nonapeptides are in the highest affinity cohort of peptides. Thus, even when multiple combinations of anchor residues contribute to binding, antigenic peptides are routinely identifiable.
DiBrino
M
M
Laboratory of Molecular Structure, NIAID, National Institutes of Health, Bethesda, Maryland 20892.
Parker
K C
KC
Margulies
D H
DH
Shiloach
J
J
Turner
R V
RV
Biddison
W E
WE
Coligan
J E
JE
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017931:DNA Primers; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D015235:HLA-B Antigens / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D059909:HLA-B14 Antigen; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology
D017931:DNA Primers; D000939:Epitopes; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D014758:Viral Core Proteins; D000409:Alanine