Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.
The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.
Schönbach
C
C
Department of Tumor Biology, University of Tokyo, Japan.
Ibe
M
M
Shiga
H
H
Takamiya
Y
Y
Miwa
K
K
Nokihara
K
K
Takiguchi
M
M
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D005434:Flow Cytometry; D015797:HLA-B35 Antigen / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D018709:Statistics, Nonparametric
D015797:HLA-B35 Antigen; D010455:Peptides