Enhancing Mass Spectrometry-Based MHC-I Peptide Identification Through a Targeted Database Search Approach

MHC-bound peptide ligands dictate the activation and specificity of CD8+ T- cells-based and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these peptides, wherein MS/MS spectra are compared against a reference proteome.

Unfortunately, matching immunopeptide MS/MS to reference proteome databases is hindered by inflated search spaces attributed to the number of matches that need to be considered due to a lack of enzyme restriction. These large search spaces limit the efficiency with which MHC-I peptides are identified.

Here we offer a solution to this problem whereby we describe a targeted database search approach and accompanying tool SpectMHC that is based on a priori predicted MHC-I peptides (Murphy et al., J Proteome Res 16:1806-1816, 2017).