Pan-Specific Prediction of Peptide?MHC Class I Complex Stability, a Correlate of T Cell Immunogenicity

MICHAEL RASMUSSEN; EMILIO FENOY; MIKKEL HARNDAHL; ANNE BREGNBALLE KRISTENSEN; IDA KALLEHAUGE NIELSEN; MORTEN NIELSEN; SØREN BUUS

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2016

0022-1767

Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL,and insights into the mechanisms that govern peptide?MHC-I binding should facilitate our understanding of CTL biology.Peptide?MHC-I interactions have traditionally been quantified by the strength of the interaction, that is, the binding affinity,yet it has been shown that the stability of the peptide?MHC-I complex is a better correlate of immunogenicity compared withbinding affinity. In this study, we have experimentally analyzed peptide?MHC-I complex stability of a large panel of human MHC-Iallotypes and generated a body of data sufficient to develop a neural network?based pan-specific predictor of peptide?MHC-Icomplex stability. Integrating the neural network predictors of peptide?MHC-I complex stability with state-of-the-art predictorsof peptide?MHC-I binding is shown to significantly improve the prediction of CTL epitopes. The method is publicly available athttp://www.cbs.dtu.dk/services/NetMHCstabpan.