immunopeptidomics-isolation-mouse-human-mhc-class-i-ii-associated

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Immunopeptidomics is an emerging field that fuels and guides the development of vaccines and immunotherapies. More specifically, it refers to the science ...

CHU Sainte-Justine Research Center

Université de Montréal

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.

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

Mass spectrometry has emerged as the method of choice for the exploration of the immunopeptidome. Insights from the immunopeptidome promise novel cancer therapeutic approaches and a better understanding of the basic mechanisms of our immune system. To meet the computational demands from the steady gain in popularity and reach of mass spectrometry-based immunopeptidomics analysis, we created the SysteMHC Atlas project, a first-of-its-kind computational pipeline and resource repository dedicated to standardizing data analysis and public dissemination of immunopeptidomic datasets.

The SysteMHC Atlas: a Computational Pipeline, a Website, and a Data Repository for Immunopeptidomic Analyses.

The rapid, global dispersion of SARS-CoV-2 has led to the emergence of a diverse range of variants. Here, we describe how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic. We analyzed a total of 330,246 high-quality SARS-CoV-2 genome assemblies, sampled across 143 countries and all major continents from December 2019 to December 2020 before mass vaccination or the rise of the Delta variant. We observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family; this is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7-supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8 T cell immunosurveillance during the first year of the pandemic.

Etienne Caron

CHU Sainte-Justine Research Center

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis