Binding of peptides to MHC class I molecules is a prerequisite for their recognition by
cytotoxic T cells. Consequently, identification of peptides that will bind to a given
MHC molecule must constitute a central part of any algorithm for prediction of T-cell
antigenic peptides based on the amino acid sequence of the protein. Development of
predictive algorithms based on experimental binding data requires experimental testing of a
very large number of peptides. A complementary approach relies on the structural conservation
observed in crystallographically solved peptide-MHC complexes. By this approach, the peptide
structure in the MHC groove is used as a template upon which peptide candidates are threaded,
and their compatibility to bind is evaluated by statistical pairwise potentials. Our original
algorithm based on this approach used the pairwise potential table of Miyazawa & Jernigan
(1996, J Mol Biol 256:623), and succeeded to correctly identify good binders only for MHC molecules
with hydrophobic binding pockets, probably because of the high emphasis of
hydrophobic interactions in this table.
Altuvia, Y., Schueler, O. and Margalit, H. 1995, J.Mol.Biol. 249:244; Altuvia Y., Sette A., Sidney J., Southwood S. and Margalit H. 1997, Hum Immunol 58:1
A recently developed pairwise potential table by Betancourt & Thirumalai (1999, Protein Sci 8:361) that is based on the Miyazawa & Jernigan
table describes the hydrophilic interactions more appropriately. Using this table the algorithm
can be applied to a wider range of MHC molecules.
Schuler-Furman O., Altuvia Y., Sette A., Margalit H. 2000, Protein Sci 9:1838.
In practice a coefficient table of 20 X L is generated, where L is the peptide length.
Each table entry represents the energy interaction of one peptide residue with its MHC contacting residues, and provides a coefficient that represents the contribution of this residue to the binding.
Choose MHC allele and peptide length via the "Choose MHC allele and peptide length" menu
The default value is "A_0201-9 (nonamers)". (The choice of the molecule
determines which coefficient table the scoring program uses on your sequence.)
Enter the sequence of the protein to be searched. Either type in the sequence or paste it in from another window. For the format see formats
By default the program ranks all the peptides. If you are interested only in the subset of peptides that contain the known HLA-motif choose the "show motif" button. The motifs are defined as broadly as possible. For motif list see motif list
Submit the job by clicking on the "submit" button.
The current maximum size of the input sequence is arbitrarily set
to 5000 residues. Longer sequences will result in an error message.
If you must run it on a longer sequence please contact us.
There are basically two types of outputs "whole protein" and "peptides with motif only"
both formats share the following information:
peptides sequence
peptide start position in protein
peptide "energy score" value.
In both formats the peptides are ranked according to their energy score (the lower the better):
In the "whole protein format all the protein peptides are ranked.
peptides with the MHC binding motif are highlighted
In the "peptides with motif only" format peptides are ranked within the group
of the peptides which fulfill the mhc binding motif.
Altuvia, Y., Schueler, O. and Margalit, H. (1995) Ranking Potential Binding Peptides to MHC Molecules by a Computational Threading Approach. J.Mol.Biol. 249:244
Altuvia Y., Sette A., Sidney J., Southwood S. and Margalit H. (1997) A Structure - Based Algorithm to predict Potential Binding Peptides to MHC Molecules with Hydrophobic Binding Pockets. Hum. Immunol. 58:1
Schuler-Furman O., Altuvia Y., Sette A., Margalit H. Structure-Based Prediction of Binding Peptides to MHC Class I Molecules: Application to a Broad Range of MHC Alleles. Protein Sci (in press)
Miyazawa S, Jernigan RL. (1996) Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. J Mol Biol. 1996 256:623
Miyazawa S, Jernigan RL. (1985) Estimation of effective interresidue contact energies from protein crystal structures: Quasi-chemical approximation. Macromolecules 18:534
Betancourt MR, Thirumalai D. (1999) Pair potentials for protein folding: choice of reference states and sensitivity of predicted native states to variations in the interaction schemes. Protein Sci 8:361