Prediction of High Affinity HLA-A2 - Binding Peptides
Normally functioning cells process and continually present on their surface, short peptides bound to class I major histocompatibility complex (MHC) molecules. When the peptides are products of a foreign genome, such as the genome of a virus that has infected the cell, the complex is recognized by cytotoxic T cells, and a series of events is triggered, which terminates in cell death. The ability to determine which protein segments will bind particular MHC molecules with high affinity is therefore of importance for the development of peptide vaccines.
We introduce a new method based on linear programming for predicting HLA-A2 binding peptides. The method has a sensitivity ~ 0.75, and specificity ~ 0.90 based upon a jack-knife procedure. The major approximation is that contribution of each position to the overall binding free energy depends only on the amino acid at that position. The database employed to develop the method uses the binding affinities for 536 9-residue-long peptides and 457 10-residue-long peptides.