Polarity of the P1 anchor residue determines peptide binding specificity between HLA-A*3101 and HLA-A*3303.
A previous pool sequence analysis showed that HLA-A*3101 and HLA-A*3303 binding peptides have the same anchor residues at P2 and the C-terminus, the only difference being that HLA-A*3303 binding peptides have two additional P2 anchor residues. Using a stabilization assay with RMA-S transfectants expressing HLA-A*3101 and human beta2-microglobulin, we tested the binding of 232 8- to 11-mer peptides carrying HLA-A*3303 anchor residues to HLA-A*3101. One hundred of these peptides (43.1%) bound to HLA-A*3101, confirming that these residues are also anchors for HLA-A*3101. Although aromatic hydrophobic P2 residues were previously shown to be stronger anchors than aliphatic hydrophobic P2 residues in HLA-A*3303 binding peptides, we detected no significant difference in HLA-A*3101 binding affinity between peptides carrying aromatic or aliphatic hydrophobic P2 residues. Statistical analysis previously showed a positive effect of negatively charged P1 residues and a negative effect of positively charged P1 residues for peptide binding to HLA-A*3303. In contrast such analysis demonstrated a positive effect of positively charged P1 residues and a negative effect of negatively charged P1 residues for peptide binding to HLA-A*3101. Analysis using mutated peptides confirmed these results. The present study therefore demonstrates that peptide binding specificity between HLA-A*3101 and HLA-A*3303 is determined by the polarity of the P1 anchor residue.
Takiguchi
M
M
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Matsuda
T
T
Tomiyama
H
H
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000276:immunology; D004563:Electrochemistry; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D014162:Transfection
D000596:Amino Acids; D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; C069527:HLA-A31 antigen