MAPPP
Information and Hyperlinks
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MAPPPInformation and Hyperlinks |
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Aim - Cleavage prediction - MHC binding prediction - References - Acknowledgements - Contacts - Links - Further reading - Instructions - MAPPP main page
MAPPP (MHC-I Antigenic Peptide Processing Prediction) will predict possible antigenic peptides to be processed and finally presented on the cell surfaces. It aides the prediction of immunodominant T-cell epitopes.
The processing and transporting is known to take multiple pathways:
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Cytoplasmic proteins are fragmented by the proteasomal processing. The transport of the fragments to the ER by TAP or alternative transport mechanisms. In the ER, further trimming of the peptides may occur. If the peptides are correct sized, the bind to MHC class I molecules. The MHC/peptide-complex takes its way to the cell surface. Here, the antigenic peptide is presented to the T-cells. If the antigens are not recognized by T-cells, they are degraded. |
At the moment, we are able to predict the proteasomal cleavage of proteins into smaller fragments, and the binding of peptide sequences to MHC class I molecules. MAPPP first generates a probability for the cleavage of each possible peptide from a protein by the proteasome in the cell.
This probability is based on a statistic-empirical method developed by H.-G. Holzhütter et al. Peptides with the highest probabilities are then given a score reflecting their abibility of binding to MHC molecules, which will transport the peptide to the cell surface. This binding score employs coefficient tables deduced from the literature by Kenneth Parker.
While there are some programs available for calculating a MHC-binding score, and a non-web-based sheet for the cleavage probability prediction was developed, none of them is able to handle a sequence of multiple proteins. We wanted to combine these two steps and have the possibility to process even an entire genome beginning with its translation into proteins, the cleavage prediction all the way through the MHC-binding scores.
For calculating the cleavage probability of a specific fragment, we first determine the probability of a cut after each of the residues within the sequence.
By limiting the minimum probability for a single residue in the form, one can limit the number of resulting possibilities.
After that, a cleavage probability for all possible fragments between two cut-sites and with the right length (choosable in the form) is calculated.
The cleavage probability for a fragment depends on the probability of either the N- and the C-residue, as well as the probabilities of the residues between these sites.
The flanking regions to the left and the right of a fragment and the probabilities of their residues are considered too.
If you use the Proteasome cleavage prediction program by itself, some further data is shown, together with the output mentioned above.
At the bottom, all the protein sequences are listed, together with the cleavage probability for each amino acid (as a hyperlink, just move the mouse on the residue; if the probability is below the specified minimum, none is shown) and
the number of occurances in the peptide fragments for each amino acid. Beneath this information, you can find all the peptide fragments just below their corresponding amino acids in the sequence.
The program uses the algorithms first implemented in FRAGPREDICT, a computer program for the prediction of proteasomal cleavage sites and proteolytic fragments, developed by H.-G. Holzhütter et al.
Alternatively, you can choose that MAPPP uses the prediciton algorithms of PaProC, developed by H.-G. Rammensee et al.
The prediction of the peptides binding to MHC class I molecules is based on a score calculated for each subsequence. Each specific amino acid at a specific position within a subsequence is given a value. Depending on the algorithms selected in the form, the values for the 8 to 10 amino acids are then multiplied (BIMAS) or added (SYFPEITHI) to determine the score for the subsequence.
These values have been pre-calculated and stored in static matrices. The pre-calculation was done by the BIMAS- and SYFPEITHI-staff.
Max-Planck-Institute for Infection Biology - MAPPP main page