Prediction Of Th Cell Epitopes Based On ISC-SVR Method

Exogenous antigen proteins are absorbed by antigen presenting cells(APC) and translated into lysosome in which they are degraded into short peptides with different length. A fragment called class â…¡-associated invariant chain peptide(CLIP) lodges in the peptide-binding groove after the Ii chain is progressively degraded by lysosomal proteases. With the help of HLA-DM molecule, CLIP is removed from the binding groove of MHC class â…¡ molecule, which makes the degraded peptides enter into the empty binding groove to form steady peptide-MHC class â…¡ complexes. The peptide-MHC class â…¡ complexes are ultimately trafficked to the cell surface to be recognized by CD4+T cell surface receptor (TCR). This process can activate Th cells to secrete cell factors that promote CTL cells to kill target cells specifically or assist B cells to make antibody against bacteria. Activation of Th cells has important supplementary effect on the cellular immunity and humoral immunity function. In this paper, the support vector regression method combined with iterative self-consistent strategy(ISC-SVR) were used to build the models to predict affinities of exogenous antigen peptides binding to MHC class â…¡ molecules. In order to improve the predictive performance, the predictive models were based on13mer extended core binding sequence rather than traditional9mer core binding sequence. We computed the affinity of MHC class â…¡ molecule binding to peptide with four methods, which were the mean method, the max method, the combine method and the eave method respectively. The predictive performance of the ISC-SVR model is validated on data sets of17MHC class â…¡ alleles. The results show that the model has certain rationality and accuracy in T cell epitopes prediction. Compared to other predictive models with the same data set, the predictive performance of our model is more satisfying. For each MHC class â…¡ allele, the ISC-SVR model got the best AUC value which was used to measure the predictive performance. Furthermore, for HLA DRB1*0101molecule, we obtained the specificities of MHC class â…¡ molecule binding to peptides which were consistent with previous experimental results.