The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases

Mol Cell Proteomics. 2020 Jan;19(1):31-49. doi: 10.1074/mcp.R119.001743. Epub 2019 Nov 19.

Abstract

The science that investigates the ensembles of all peptides associated to human leukocyte antigen (HLA) molecules is termed "immunopeptidomics" and is typically driven by mass spectrometry (MS) technologies. Recent advances in MS technologies, neoantigen discovery and cancer immunotherapy have catalyzed the launch of the Human Immunopeptidome Project (HIPP) with the goal of providing a complete map of the human immunopeptidome and making the technology so robust that it will be available in every clinic. Here, we provide a long-term perspective of the field and we use this framework to explore how we think the completion of the HIPP will truly impact the society in the future. In this context, we introduce the concept of immunopeptidome-wide association studies (IWAS). We highlight the importance of large cohort studies for the future and how applying quantitative immunopeptidomics at population scale may provide a new look at individual predisposition to common immune diseases as well as responsiveness to vaccines and immunotherapies. Through this vision, we aim to provide a fresh view of the field to stimulate new discussions within the community, and present what we see as the key challenges for the future for unlocking the full potential of immunopeptidomics in this era of precision medicine.

Keywords: HLA/MHC; IWAS; Immunology; cancer therapeutics; immunopeptidome; infectious disease; mass spectrometry; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / therapy*
  • Cohort Studies
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Immunotherapy
  • Infections / diagnosis
  • Infections / therapy
  • Mass Spectrometry
  • Neoplasms / diagnosis
  • Neoplasms / therapy
  • Peptides / chemistry*
  • Peptides / immunology*
  • Precision Medicine
  • Prognosis

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptides