Immunopeptidomics is a specialized branch of proteomics focused on the large-scale identification and characterization of peptides presented by major histocompatibility complex (MHC) molecules on the surface of cells. These peptides, known as the immunopeptidome, are central to immune surveillance because they are recognized by T cells, enabling the immune system to detect infected or malignant cells.

Key Aspects of Immunopeptidomics

• Purpose: Immunopeptidomics enables the identification of both canonical and noncanonical peptides (including neoantigens) presented by MHC molecules, which is crucial for understanding immune responses, developing immunotherapies (especially cancer immunotherapy), vaccine design, and studying autoimmune diseases.

• Technique: The process typically involves:
• Isolating MHC-peptide complexes from cells or tissues using MHC-specific antibodies.
• Eluting the bound peptides, often with mild acid treatment.
• Purifying the peptides using chromatographic methods.
• Analyzing the peptides by high-resolution mass spectrometry.
• Using advanced bioinformatics to match mass spectra to peptide sequences.

• Applications:
• Cancer: Identification of tumor-specific antigens and neoantigens to guide personalized immunotherapies and vaccine development.
• Autoimmunity: Discovery of autoantigens and understanding mechanisms of autoimmune diseases, including cross-reactivity and post-translational modification-driven changes in antigenicity.
• Infectious Disease: Mapping pathogen-derived peptides to inform vaccine and diagnostic development.

• Challenges: Immunopeptidomics faces technical hurdles such as the low abundance of MHC-bound peptides, the need for large sample amounts, and the complexity of data analysis.

Translational Impact

Immunopeptidomics has already contributed to:

• Personalized cancer immunotherapies by identifying patient-specific tumor antigens.
• Biomarker discovery for early detection and monitoring of diseases.
• Advances in computational epitope prediction, improving the design of diagnostics and therapeutics for immune-related diseases.

In summary, immunopeptidomics is transforming our understanding of antigen presentation and immune recognition, with broad implications for precision medicine, immunotherapy, and the study of immune-mediated diseases.