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Information on SYFPEITHI

General information

Specific information on MHC motifs included in the database

References mentioned in the database, but not included in Pubmed

Details on motifs included in the database

SYFPEITHI and its scores

Submitting new MHC motifs, ligands and T-cell epitopes

Links to MHC relevant sites

General information

The database is based on previous publications on T-cell epitopes and MHC ligands.

Since the number of motifs continuously increases, it was necessary to set up a database which facilitates the search for peptides and allows the prediction of T-cell epitopes. The prediction is based on published motifs (pool sequencing, natural ligands) and takes into consideration the amino acids in the anchor and auxiliary anchor positions, as well as other frequent amino acids. The score is calculated according to the following rules: The amino acids of a certain peptide are given a specific value depending on whether they are anchor, auxiliary anchor or preferred residue. Ideal anchors will be given 10 points, unusual anchors 6-8 points, auxiliary anchors 4-6 and preferred residues 1-4 points. Amino acids that are regarded as having a negative effect on the binding ability are given balues between -1 and -3.

Howto cite the database:

Hans-Georg Rammensee, Jutta Bachmann, Niels Nikolaus Emmerich, Oskar Alexander Bachor, Stefan Stevanovic: SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics (1999) 50: 213-219 (access via : www.syfpeithi.de)

An X in peptide sequences stands for an undetermined amino acid. However, if the peptide sequence has been determined by mass spectometry, as is the case for the peptides reported by Hunt and co-workers, X stands for either Leu or Ile (which have the same mass).

As far as T-cell epitopes are concerned, only those have been selected which are likely to be naturally processed.

From the numerous class II motifs that have been published, we selected the more convincing ones, i.e. those compatible with class II structure. Due to the variable number of amino acids between the N-terminus and the first anchor of peptides, alignment of ligands or T-cell epitopes to class II motifs is always arbitrary, unless a structural analysis has been performed. In case of class II ligands occurring as nested sets, we included only one or a few members of the set in many cases.
 

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Specific information on MHC motifs included in the database

References without link to Pubmed:

Brander and Walker 1996: Brander, C. and Walker, B. The HLA-class I CTL response in HIV-1 infection: Identification of optimal epitopes, Los Alamos, New Mexico: Los Alamos National Laboratory, Theoretical Biology and Biophysics 1996

Stevanovic et al. 1995: Stevanovic, S., Pomer, S., and Rammensee, H.-G. Oberflächenantigene im Nierenzellkarzinom - Präsentation von MHC I-gebundenen Selbstpeptiden. Akt. Urol. Sonderheft (26): 45-46, 1995

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Details on motifs included in the database:

RT1.Aa (TAP2A-associated): Residues were determined by acid elution and pool sequencing of bound peptides following in vitro refolding of the recombinant alpha chain around a random peptide library.

RT1.Aa (TAP2B-associated): Residues were determined by acid elution and pool sequencing of bound peptides following in vitro refolding of the recombinant alpha chain around a random peptide library.

Mafa-A2: T-cell epitope determined by serological methods

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SYFPEITHI and its scores

The scoring system evaluates every amino acid within a given peptide. Individual amino acids may be given the arbitrary value 1 for amino acids that are only slightly preferred in the respective position, optimal anchor residues are given the value 15; any value between these two is possible. Negative values are also possible for amino acids which are disadvantageous for the peptide's binding capacity at a certain sequence position. The allocation of values is based on the frequency of the respective amino acid in natural ligands, T-cell epitopes, or binding peptides. Further explanations on the algorithm can be found in HG Rammensee, J Bachmann, NPN Emmerich, OA Bachor and S Stevanovic (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50: 213-219

Our main aim is to have an extremely reliable SYFPEITHI epitope prediction algorithm.  Therefore, only those MHC class I alleles for which a large amount of data is available are included in the "epitope prediction" section of SYFPEITHI. A reliability of at least 80% in retrieving the most apt epitope can be expected. Thus the naturally presented epitope should be among the top-scoring 2 % of all peptides predicted in 80 % of all predictions. For example, if a protein sequence is as long as 400 amino acids, it can be split into 392 possible nonameric peptides. Therefore, the correct epitope should then be among the 8 top-scoring peptides.

For epitope predictions using MHC class II motifs high reliabilities usually cannot be achieved because of the more variable pocket binding behavior. We estimate a  reliability of approximately 50% only.

Please note:

· Different MHC class I molecules prefer a different length of ligands. For example, SYFPEITHI offers predictions for H2-Kb octamers, HLA-A*0201 nonamers and decamers, or HLA-B8 octamers and nonamers.
· The maximal scores vary between different MHC alleles. Therefore, we advise you to include known ligands/epitopes in order to have an approximation of the scoring. For example, the maximal score for HLA-A*0201 peptides is 36. The well-known epitope GILGFVFTL derived from the influenza A matrix protein scores 30.
· All predicted MHC class II ligands are 15mers, consisting of three N-terminal flanking residues, the nonamer core sequence located within the binding groove, and three C-terminal flanking residues. Thus, anchor residue P1 appears in position 4 of the peptides predicted with "SYFPEITHI".
 

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Submitting new MHC Motifs, ligands and T-cell epitopes

We pursue the retrieval of newly published epitopes and ligands in international reports. But we are sure that some will unintentionally escape our attention. In collecting the data covered, we tried to be as accurate and as comprehensive as possible. Given the vast amount of data to be screened, however, we are afraid that some MHC ligands or even motifs have been omitted inadvertently. We apologize in advance for this and also for any errors that were overlooked in spite of very thorough cross-checking!

... and would be grateful for any new motifs you discovered or errors you found

 


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Useful links