Y. Altuvia et al., A STRUCTURE-BASED ALGORITHM TO PREDICT POTENTIAL BINDING PEPTIDES TO MHC MOLECULES WITH HYDROPHOBIC BINDING POCKETS, Human immunology, 58(1), 1997, pp. 1-11
Binding of peptides to MHC class I molecules is a prerequisite for the
ir recognition by cytotoxic T cells. Consequently, identification of p
eptides that will bind to a given MHC molecule must constitute a centr
al part of any algorithm for prediction of T-cell antigenic peptides b
ased on the amino acid sequence of the protein. Binding motifs, define
d by anchor positions only, have proven to be insufficient to ensure b
inding, suggesting that other positions along the peptide sequence als
o affect peptide-MHC interaction. The second phase of prediction schem
es therefore take into account the effect of all positions along the p
eptide sequence, and are based on position-dependent-coefficients that
are used in the calculation of a peptide score. These coefficients ca
n be extracted from a large ensemble of binding sequences that were te
sted experimentally, or derived from structural considerations, as in
the algorithm developed by us recently. This algorithm uses the coordi
nates of solved complexes to evaluate the interactions of peptide amin
o acids with MHC contact residues, and results in a peptide score that
reflects its binding energy. Here we present our analysis for peptide
binding to four MHC alleles (HLA-A2, HLA-A68, HLA-B27 and H-2K(b)), a
nd compare the predictions of the algorithm to experimental binding da
ta. The algorithm performs successfully in predicting peptide binding
to MHC molecules with hydrophobic binding pockets but not-when MHC mol
ecules with hydrophilic, charged pockets are considered. For MHC molec
ules with hydrophobic pockets it is demonstrated how the algorithm suc
ceeds in distinguishing binding from non-binding peptides, and in high
ranking of immunogenic peptides within all overlapping same-length pe
ptides spanning their respective protein sequences. The latter propert
y of the algorithm makes it a useful tool in the rational design of pe
ptide vaccines aimed at T-cell immunity. (C) American Society for Hist
ocompatibility and Immunogenetics, 1997. Published by Elsevier Science
Inc.