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Open Access Research article

Flanking p10 contribution and sequence bias in matrix based epitope prediction: revisiting the assumption of independent binding pockets

Christian S Parry

Author Affiliations

Computational Biophysics Section, Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-9314, USA

BMC Structural Biology 2008, 8:44  doi:10.1186/1472-6807-8-44

Published: 16 October 2008



Eluted natural peptides from major histocompatibility molecules show patterns of conserved residues. Crystallographic structures show that the bound peptide in class II major histocompatibility complex adopts a near uniform polyproline II-like conformation. This way allele-specific favoured residues are able to anchor into pockets in the binding groove leaving other peptide side chains exposed for recognition by T cells. The anchor residues form a motif. This sequence pattern can be used to screen large sequences for potential epitopes. Quantitative matrices extend the motif idea to include the contribution of non-anchor peptide residues. This report examines two new matrices that extend the binding register to incorporate the polymorphic p10 pocket of human leukocyte antigen DR1. Their performance is quantified against experimental binding measurements and against the canonical nine-residue register matrix.


One new matrix shows significant improvement over the base matrix; the other does not. The new matrices differ in the sequence of the peptide library.


One of the extended quantitative matrices showed significant improvement in prediction over the original nine residue matrix and over the other extended matrix. Proline in the sequence of the peptide library of the better performing matrix presumably stabilizes the peptide conformation through neighbour interactions. Such interactions may influence epitope prediction in this test of quantitative matrices. This calls into question the assumption of the independent contribution of individual binding pockets.