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

Prathyusha Konda1, J Patrick Murphy2, Morten Nielsen3,4

  • 1Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.

Methods in Molecular Biology (Clifton, N.J.)
|August 1, 2019
PubMed

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).

Keywords:
BioinformaticsImmuno-informaticsMHC ligandomeMHC peptidesMass spectrometryNetMHCSpectMHC

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