The role of anchor residues in the binding of peptides to HLA-A*1101 molecules

The binding of 136 8- to la-mer peptides carrying anchor residues at positi on 2 (P2) and the C-terminus to HLAl-A*1101 molecules was analyzed by a sta bilization assay using RMA-S transfectants expressing HLA-A*1101 and human beta(2)-microglobulin. 72.1% of these peptides bound to HLA-A*1101 molecule s. Two known HLA-A11-restricted cytotoxic T-lymphocyte epitope peptides sho wed high affinity to HLA-A*1101. The results confirmed a previous pool sequ encing study of HLA-A*1101 binding self-peptides, which showed that Lys at the C-terminus and Val, ne, 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 an d Tyr. In addition, hydrophobic residues Leu, Phe, Tyr, Ile, and Ala at pos ition 3 (P3) are secondary anchors but are weaker than those at P2. The aff inities of the 8- and 12-mer peptides were significantly lower than those o f 9- to Il-mer peptides, There was however no difference in affinity betwee n 9-, 10- and Il-mer peptides, Furthermore, the analysis using peptides mut ated at the C-terminus showed that HLA-A*1101 molecules can bind peptides c arrying another positively charged residue, Arg. The present study clarifie d the role of the anchor residues at P2, P3 and the C-terminus in the bindi ng of HLA-A*1101 molecules.