Predicting peptides bound to I-Ag7 class II histocompatibility molecules using a novel expectation-maximization alignment algorithm.
The useful structural features of class II MHC molecules are rarely integrated into T-cell epitope predictions. We propose an approach that applies a novel expectation-maximization algorithm to align the naturally processed peptides selected by the class II MHC I-A(g7) molecule - focusing on the five MHC-specific anchor positions. Based on the alignment profile, log of odds (LOD) scores supplemented with the Laplace plus-one pseudocounts method are applied to identify the potential T-cell epitopes. In addition, an innovative computational concept of hindering residues using statistical and structural information is developed to refine the prediction. Performance analysis by receiver operating characteristics statistics and the experimental validation of the LOD scores demonstrate the accuracy of our predictive model. Furthermore, our model successfully predicts T-cell epitopes of hen egg-white lysozyme protein antigen. Our study provides a framework for predicting T-cell epitopes in class II MHC molecules.
Chang
Kuan Y
KY
Computational Biology Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
Suri
Anish
A
Unanue
Emil R
ER
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008126:Lod Score; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000502:physiology; D016415:Sequence Alignment
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D010455:Peptides