T Cell Epitopes - MHC I Processing Prediction Tools Description

The T Cell MHC I Processing Prediction tools can be found at http://tools.immuneepitope.org/analyze/html/mhc_processing.html.

Proteasomal cleavage/TAP transport/MHC class I combined predictor

For the prediction of antigen processing through the MHC class I antigen presentation pathway, we incorporated predictions of proteasomal cleavage and TAP transport similar to the MHCPathway website described in (Tenzer et al, CMLS, 2005).  The predictions are based on in vitro experiments characterizing the sequence specificity of proteasomal cleavage and TAP transport.  The goal of the prediction is to identify MHC-I ligands (peptides that are naturally processed from their source proteins and presented by MHC class I molecules).

The proteasomal cleavage predictions evaluate how efficiently a peptide or its N-terminally prolonged precursors can be liberated from its source protein.  The TAP transport predictions evaluate how efficiently a peptide or its N-terminal prolonged precursors are transported into the ER by TAP (Peters et al., Immunol, 2003).  When this information is taken together and combined with MHC class I binding predictions, the tool yields a prediction of the efficiency with which a peptide is presented on the cell surface.  The methods available are ANN, SMM, ARB, SMMPMBEC, Comblib, NetMHCpan, which are described in T Cell Epitopes - MHC Class I Binding Prediction Tools Description.

A check box can be selected to show only frequently occurring alleles.  This allows the selection of only those alleles that occur in at least 1% of the human population or allele frequency of 1% or higher.  However, un-checking the check-box will allow selection of all the alleles and corresponding peptide lengths for a particular species.  Users can also upload an allele file instead of entering allele on the page one at a time. 

Neural network based prediction of proteasomal cleavage sites (NetChop) and T cell epitopes (NetCTL)

NetChop produces neural network predictions for cleavage sites of the human proteasome (Kesmir et al., 2002).  NetChop takes into account the characteristics of the structurally modified proteasomes found in cells stimulated by gamma-interferon under physiological conditions.  The NetChop algorithm was trained on in vitro data and MHC Class I ligand data.  The use of this training set, combined with the artificial neural network methodology, makes the prediction of cleavage sites more accurate.  NetChop has been trained only on human data, but since the proteasome structure is quite conserved, the algorithm developers believe that the tool is capable of making reliable predictions for at least the other mammalian proteasomes.

NetCTL predicts CTL epitopes in protein sequences integrating prediction of peptide MHC binding, proteasomal C terminal cleavage and TAP transport efficiency.  The method is described in detail in Larsen et al. (Eur J Immunol., 2005).  NetCTLpan is an update to the original NetCTL server that allows for prediction of CTL epitope with restriction to any MHC molecules of known protein sequence (Stranzl et al., Immunogenetics, 2010).