IMBAS-MS Discovers Organ-Specific HLA Peptide Patterns in Plasma

Area of Science:

• Immunology
• Proteomics
• Biomarker Discovery

Background:

• The immune system distinguishes self from non-self via peptide presentation by human leukocyte antigen (HLA) proteins.
• While tissue-based immunopeptidomics is established, the origin and biomarker potential of HLA peptides in plasma (soluble HLA or sHLA) remain underexplored.
• Current immunopeptidomics methods lack sensitivity and require large plasma volumes, limiting their clinical applicability.

Purpose of the Study:

• To develop a highly sensitive, automated, and economical workflow for analyzing HLA peptides in plasma.
• To investigate the plasma immunopeptidome and its potential for biomarker discovery.

Main Methods:

• Development of Immunopeptidomics by Biotinylated Antibodies and Streptavidin (IMBAS) coupled with mass spectrometry (MS).
• Optimization of a workflow enabling high-throughput and sensitive quantification of HLA peptides.
• Analysis of plasma samples from healthy donors.

Main Results:

• IMBAS-MS quantifies over 5000 HLA class I peptides from a small plasma volume (200 μl) within 30 minutes.
• The plasma immunopeptidome in healthy individuals is stable year-round and shows strong correlation between individuals with shared HLA types.
• Peptides from various tissues, including the brain, are proportionally represented in the plasma.

Conclusions:

• Soluble HLA (sHLA) peptides in plasma represent a promising, readily accessible source for immunological research.
• The developed IMBAS-MS workflow significantly enhances sensitivity and efficiency for plasma immunopeptidomics.
• sHLA peptides hold potential for future biomarker discovery, particularly in precision oncology.