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

MURPHY, J. PATRICK; NIELSEN, MORTEN; KONDA, PRATHYUSHA; GUJAR, SHASHI

METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.)

Humana Press Inc.

Año: 2019 vol. 2024 p. 301 - 307

1064-3745

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).