The role of anchor residues in the binding of peptides to HLA-A*1101 molecules.
The binding of 136 8- to 12-mer peptides carrying anchor residues at position 2 (P2) and the C-terminus to HLA-A*1101 molecules was analyzed by a stabilization assay using RMA-S transfectants expressing HLA-A*1101 and human beta2-microglobulin. 72.1% of these peptides bound to HLA-A*1101 molecules. Two known HLA-All-restricted cytotoxic T-lymphocyte epitope peptides showed high affinity to HLA-A*1101. The results confirmed a previous pool sequencing study of HLA-A*1101 binding self-peptides, which showed that Lys at the C-terminus and Val, Ile, Phe, Tyr, and Thr at P2 are anchor residues for HLA-A*1101. Thr and aliphatic hydrophobic residues Val, Ile, and Leu at P2 are stronger anchor residues than the aromatic hydrophobic residues Phe and Tyr. In addition, hydrophobic residues Leu, Phe, Tyr, Ile, and Ala at position 3 (P3) are secondary anchors but are weaker than those at P2. The affinities of the 8- and 12-mer peptides were significantly lower than those of 9- to 11-mer peptides. There was however no difference in affinity between 9-, 10- and 11-mer peptides. Furthermore, the analysis using peptides mutated at the C-terminus showed that HLA-A*1101 molecules can bind peptides carrying another positively charged residue, Arg. The present study clarified the role of the anchor residues at P2, P3 and the C-terminus in the binding of HLA-A*1101 molecules.
Chujoh
Y
Y
Department of Tumor Biology, Institute of Medical Science, University of Tokyo, Japan.
Sobao
Y
Y
Miwa
K
K
Kaneko
Y
Y
Takiguchi
M
M
D001665:Binding Sites; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059870:HLA-A11 Antigen; D006801:Humans; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D010455:Peptides