title: Building proteomic tool boxes to monitor MHC class I and class II peptides.
abstract: Major histocompatibility complex Class I (MHCI) and Class II (MHCII) presented peptides powerfully modulate T cell immunity and play a vital role in generating effective anti-tumor and anti-viral immune responses in mammals. Characterizing these MHCI or MHCII presented peptides can help generate therapeutic treatments, afford information on T cell mediated biomarkers, provide insight into disease progression, and reduce adverse anti-drug side effects from engineered biotherapeutics. Here, we explore the tools and techniques commonly employed to discover both MHCI- and MHCII-presented peptides. We describe complementary strategies that enhance the characterization of these peptides and the informatics tools employed for both predicting and characterizing MHCI- and MHCII-presented epitopes. The evolution of methodologies for isolating MHC-presented peptides is discussed, as are the mass spectrometric workflows that can be employed for their characterization. We provide a perspective on where this field is headed, and how these tools may be applicable to the discovery and monitoring of epitopes in a variety of scenarios.
authors.affiliation: Department of Proteomics & Biological Resources, Genentech Inc., San Francisco, CA, USA.
authors.forename: Frances-Rose
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Department of Cancer Immunology, Genentech Inc., San Francisco, CA, USA.
authors.forename: Lélia
authors.initials: L
authors.lastname: Delamarre
authors.affiliation: Department of Bioinformatics & Computational Biology, Genentech Inc., San Francisco, CA, USA.
authors.forename: Suchit
authors.initials: S
authors.lastname: Jhunjhunwala
authors.affiliation: Department of Molecular Biology, Genentech Inc., San Francisco, CA, USA.
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.affiliation: Department of Proteomics and Biological Resources, Genentech Inc., San Francisco, CA, USA.
authors.forename: Qui T
authors.initials: QT
authors.lastname: Phung
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, San Francisco, CA, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Elias
authors.affiliation: Department of Proteomics & Biological Resources, Genentech Inc., San Francisco, CA, USA.
authors.forename: Jennie R
authors.initials: JR
authors.lastname: Lill
mesh_terms: D000818:Animals; D000939:Epitopes / Q000737:chemistry; D059014:High-Throughput Nucleotide Sequencing; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides
keywords: Biomedicine; Cancer vaccines; Major histocompatibility complex; Next generation sequencing; T cell epitope