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T-cell Epitope Prediction Tools
There are several approaches possible when predicting T-epitopes, particularly CTL epitopes. Most of them are related to the prediction of a peptide's ability to bind the groove of MHC molecules, indicating that it can be presented in the context of MHC I or II respectively.
However, less than 5% of peptides binding to MHC demonstrate ANY biological activity, even less being strong, functional epitopes.
In contrast to other programs EpiQuest-T predicts areas in the molecule that are likely to contain strong, functional, immunodominant CTL epitopes.
EpiQuest-T is based on our unique algorithm that has identified the typical structural features of a strong T-epitope that should be recognized by TCR in the context of a particular type of MHC molecule.
The software analyzes the linear protein sequence and calculates the probability of an amino acid at a given position in the sequence, depending on the context, to be involved into high affinity (immuno-dominant) CTL epitope depending on its context.
Convenient Layout and Output
The program predicts the areas likely to contain immunodominant CTL epitopes and ranks them according to their strength. The prediction is haplotype-restricted, and the peptide is recognized by TCR in the context of particular MHC which contributes to the complex recognition.
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In the example presented below of the analysis for the presence of HLA-A2 restricted CTL epitopes in an insulin sequence, we can see that the program finds several areas of potential epitopes of different strength. It well discriminates strong epitopes from both weak and negative areas, the main peak corresponding to the immunodominant CTL epitope in Insulin sequence (the known epitopes indicated below the histogram):
The results are presented as histogram and tabular results.The tabular results show relative immunogenicity (AGI) and antigenicity corrected for the length of the fragment (AGR).
As can be seen, the immunodominant epitope-containing sequence has the highest predicted score.
Selecting optimal epitopes
Additional tools we offer allow you to sort all T-epitopes according to relative immunodominance (up to 2000 selected epitopes), select the ones that are highly specific for the target molecule, or sort the epitopes according to their immunological complexity (uniqueness).
T-Scanner is based on the same algorithm and matrix as EpiQuest-T, but developed for comparing large number of epitopes, either selected by other programs (i.e. the programs predicting MHC-binding or proteolytic cleavage of the sequence in MHCI compartments) or eluted from target cells, etc.
EpiQuest-C is the program that analyses local immunological complexity of the protein sequence.
The higher is the complexity of the peptides, the higher is the probability of it being highly specific for this sequence only.
When you need to access the relative complexity for a group of already selected epitopes (isolated from sequences due to their potential T-epitope activity, or other criteria), you can easily do this for up to 2000 sequences at once using the C-Scanner application which is based on the same algorithm and values as EpiQuest-C.
Predicting the relative strength of an epitope
The program EpiQuest-T (and its T-Scanner version, more adapted for the analysis of large collections of epitopes) ascribes a value of its potential "strength" to each epitope. The Antigenicity Index (AGI) allows comparing epitopes to each other and selecting the best ones. Below we show two examples of how AGI index is related to the functional activity of CTL epitopes.
The ability to predict correctly functional activity (immunodomiance) of T-cell epitopes is the most critical difference between EpiQuest-T and other T-cell epitope- predicting programs.
All H2kB epitopes from IEDB database were divided according to their activity in functional tests, as described in the database. The AGI index was calculated by EpiQuest-T for the best 8-mer epitope within the epitope sequence (which could range from 8 to 15 amino acids). The figure above shows the values for epitopes in every group and the median value of AGI in every group. The low values for the best epitopes of H2kD haplotype show that the analysis works only for the particular haplotype, the data is MHC-restricted.