How Mass Spectrometry Proteomics Enhances Immunopeptidome Profiling

The immune system is the second most complex system in the body, second only to the brain. It keeps us healthy by recognizing and clearing dangerous pathogens or abnormal cells. Yet it can also cause damaging autoimmune conditions such as rheumatoid arthritis and multiple sclerosis. Hence there is great untapped value in the fields of immune cell profiling and immunopeptidome studies.

Despite more than a century of research, we have only recently begun to truly understand the inner workings of the immune system and how it might be harnessed to treat cancer and other diseases. Immunopeptidome profiling via mass spectrometry proteomics is a promising area of research that may help shine a light on such complex mechanisms.

The challenge of cracking the immune code is partly due to the way the immune system communicates using protein-based signals. It relies on interactions between cell-surface receptors and other molecules to trigger protective or harmful responses.

But it is only in recent years that proteomics technologies have advanced to the point where we are able to explore and catalog the complexity of these molecules and their interactions in order to understand and manipulate immune responses: an emerging field known as immunopeptidomics.

What is Immunopeptidomics?

Immunopeptidomics, also known as immunopeptidome profiling, is the study of the small fragments of proteins (peptides) presented by the Major Histocompatibility Complex (MHC) Class I and II or Human Leukocyte Antigen (HLA) receptors on the surface of cells throughout the body.

These peptides represent a sample of the cell contents, including fragments of pathogens or abnormal proteins resulting from genetic mutations in cancer cells. MHC-associated peptides are then recognized as either self or non-self by T-cell receptors, effectively ‘training’ T-cells to destroy other infected or cancerous cells that are also presenting the same unusual peptides.

This T-cell mediated response is an important line of immune defense against infectious pathogens and tumor tissue. But it also forms the basis of autoimmune diseases and allergies if the immune response is accidentally triggered by peptides presented by healthy cells.

The Advantages of Mass Spectrometry Proteomics for Immunopeptidome Profiling

Studying MHC-bound immunopeptides is challenging due to their rarity and diversity. Although there are collectively many MHC receptors in each tissue sample, there will be very few bound to each specific peptide.

Conventional proteomics technologies have therefore required large samples to fully capture the immunoepitope diversity, while technical limitations have made it difficult to reliably predict peptide fragment identity.

However, advances in mass spectrometry proteomics, pioneered by Biognosys, now make it possible to reliably identify and measure thousands of immunopeptides in a single experiment.

Our Immunopeptidome Profiling solution offers an optimized high-throughput workflow for in-depth, unbiased immunopeptidome profiling using our proprietary Hyper Reaction Monitoring™ data-independent acquisition mass spectrometry technology, together with our Spectronaut™ and Spectromine™ data analysis software.

This state-of-the-art research service allows you to reproducibly characterize more than 10,000 immunopeptides from as little as 15 mg of tissue, with the ability to scale from small lab experiments up to large clinical trials.

Importantly, mass spectrometry immunopeptidome analysis can also reveal novel immunopeptides created by genetic mutations within cancer cells (neoantigens), which represent important targets for immunotherapy. Furthermore, we can identify post-translational protein modifications such as phosphorylation, acetylation and ubiquitinylation, which also contribute to immune recognition.

Accelerate your Immunology and Immunotherapy Research with Immunopeptidome Profiling

Whether you are carrying out foundational immunology research or developing the next generation of game-changing immunotherapies, our Immunopeptidome Profiling service provides the data you need to crack the immune system’s code.

We are able to support research along every step of the immunotherapy pathway, from initial discovery research all the way through to clinical trials. Moreover, we can offer our services in a GLP and GCP compliant environment, generating regulatory-grade data to support market authorization.

Get in touch to find out how we can help you accelerate your immunotherapy research today.