M. Dibrino et al., THE HLA-B14 PEPTIDE BINDING-SITE CAN ACCOMMODATE PEPTIDES WITH DIFFERENT COMBINATIONS OF ANCHOR RESIDUES, The Journal of biological chemistry, 269(51), 1994, pp. 32426-32434
Most peptides that bind to a particular major histocompatibility compl
ex 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 t
hree of these amino acids sufficed for binding to HLA-B14 in vitro. Us
ing 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 ho
w 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 com
plexes 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.