Developing mass spectrometry-based proteomics and immunopeptidomics platforms to analyze stability profiles and PTMs in peptides bound to HLA class I molecules.

A comprehensive snapshot of immune specificity can be achieved by studying the interaction between peptide-MHC class I (pMHCI) and CD8+ T cells. Since the stability of pMHCI complexes has been postulated to influence the immunogenicity of virus-derived epitopes and cancer neoepitopes, we sought to further establish the correlation between thermostability and immunogenicity. A panel of more than 100 Vaccinia virus (VACV)-derived pMHCI with known CD8+ T cell response profiles were then used to investigate the extent to which their thermostability profiles correlated with their immunogenicity. We successfully developed two machine learning-based models to predict VACV peptide immunogenicity.