Enabling Routine MHC-II-Associated Peptide Proteomics for Risk Assessment of Drug-Induced Immunogenicity

Area of Science:

• Immunology
• Proteomics
• Mass Spectrometry

Background:

• Major histocompatibility complex-II (MHC-II)-Associated Peptide Proteomics (MAPPs) identifies peptides that can trigger T cell responses.
• Assessing drug immunogenicity requires reproducible and comparable MAPPs data across experiments and donors.

Purpose of the Study:

• To develop and validate a data processing pipeline (dataMAPPs) for robust analysis of MAPPs data.
• To enable standardized comparison of MHC-II associated peptides across different experimental conditions and biological samples.

Main Methods:

• Development of the dataMAPPs pipeline featuring heat maps (heatMAPPs) for data visualization.
• Implementation of a customized normalization procedure using endogenous peptides for signal standardization.
• Evaluation of MAPPs platform reproducibility using tool compounds and assessment of variation sources.

Main Results:

• The dataMAPPs pipeline with heatMAPPs facilitates rapid comparison of MAPPs data between conditions and donors.
• A novel normalization method ensures standardized signal intensities for cross-experimental comparability.
• Biological variability across donors significantly exceeds technical variation in MAPPs experiments.

Conclusions:

• The MAPPs platform, enhanced by dataMAPPs, provides reproducible data for preclinical immunogenicity risk assessment.
• The developed methods support the application of MAPPs in clinical settings for evaluating drug-induced immune responses.