MassIVE MSV000092747

Partial Public PXD044851

Expanding the MAPPs assay to accommodate MHC-II pan re-ceptors for improved predictability of potential T cell epitopes

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Description

The appended raw files, csv files and other documents were deposited in the public domain in support for the publication "Expanding the MAPPs assay to accommodate MHC-II pan re-ceptors for improved predictability of potential T cell epitopes" by Katharina Hartman, Guido Steiner, Michel Siegel, Cary M. Looney, Timothy P. Hickling, Katharine Bray-French, Sebastian Springer, Celine Marban-Doran and Axel Ducret. The abstract is as follows: A critical step in the immunogenicity cascade is attributed to human leukocyte antigen (HLA) II presentation triggering T cell immune responses. The liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based major histocompatibility complex (MHC) II-associated peptide proteomics (MAPPs) assay is implemented during preclinical risk assessments to identify bio-therapeutic-derived T cell epitopes. Although studies indicate HLA-DP and HLA-DQ alleles are linked to immunogenicity, most MAPPs studies are restricted to HLA-DR as the dominant HLA II genotype due to lack of well-characterized immunoprecipitating antibodies. Herein we ad-dress this issue by testing various commercially-available clones of MHC-II pan (CR3/43, WR18, and Tu39), HLA-DP (B7/21), and HLA-DQ (SPV-L3 and 1a3) antibodies in the MAPPs assay, and characterizing identified peptides according to binding specificity. Our results reveal that HLA II receptor-precipitating reagents with similar reported specificities differ based on clonality and that MHC-II pan antibodies do not entirely exhibit pan-specific tendencies. Since no individual antibody clone is able to recover the complete HLA II peptide repertoire, we recommend a mixed strategy of clones L243, WR18, and SPV-L3 in a single immunoprecipitation step for more robust compound-specific peptide detection. Ultimately, our optimized MAPPs strategy im-proves the predictability and additional identification of T cell epitopes in immunogenicity risk assessments. The dataset is divided in two sections, one supporting the figures 1-4, the other one supporting the figure 5-6. The collective data has aslo be used to generate the supplementary tables S1-S9. [doi:10.25345/C5XP6VD75] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: MAPPs assay ; immunopeptidomics ; HLA-II receptors ; anti-drug antibodies ; immunogenicity ; in silico analysis ; Adalimumab ; ATR-107 ; KLH

Contact

Principal Investigators:
(in alphabetical order) 		Axel Ducret, Roche Innovation Center Basel, Switzerland
Submitting User: ducreta

Publications

Hartman, K.; Steiner, G.; Siegel, M.; Looney, C.M.; Hickling, T.P.; Bray-French, K.; Springer, S.; Marban-Doran, C.; Ducret, A.
Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved Predictability of Potential T Cell Epitopes.
accepted for publication in Biology (2023) 12.

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