PXD044851

PXD044851 is an original dataset announced via ProteomeXchange.

Title	Expanding the MAPPs assay to accommodate MHC-II pan re-ceptors for improved predictability of potential T cell epitopes
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.
HostingRepository	MassIVE
AnnounceDate	2023-09-15
AnnouncementXML	Submission_2023-09-15_07:27:45.297.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Axel Ducret
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; Deamidated; Gln->pyro-Glu
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-25 02:45:02	ID requested
⏵ 1	2023-09-15 07:27:45	announced

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.

submitter keyword: MAPPs assay, immunopeptidomics, HLA-II receptors, anti-drug antibodies, immunogenicity, in silico analysis, Adalimumab, ATR-107, KLH

Axel Ducret
contact affiliation	Roche Innovation Center Basel
contact email	axel.ducret@roche.com
lab head
Axel Ducret
contact affiliation	F. Hoffmann-La Roche Ltd
contact email	axel.ducret@roche.com
dataset submitter

MassIVE dataset URI

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