Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.
DM
DO
HLA
MHC
antigen presentation
immunopeptidome
mass spectrometry
proteome
Journal
Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
05
03
2021
revised:
07
01
2022
accepted:
16
01
2022
pubmed:
28
1
2022
medline:
6
4
2022
entrez:
27
1
2022
Statut:
ppublish
Résumé
Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen-presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM sensitivity, peptide abundance, binding affinity and motif, peptide length, and choice of binding register along the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body.
Identifiants
pubmed: 35085787
pii: S1535-9476(22)00012-3
doi: 10.1016/j.mcpro.2022.100204
pmc: PMC10329146
pii:
doi:
Substances chimiques
HLA-D Antigens
0
HLA-DR Antigens
0
Histocompatibility Antigens Class II
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
100204Subventions
Organisme : NIAID NIH HHS
ID : R21 AI095813
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no competing interests.
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