Dataset Information

Tuning DO:DM ratios modulates HLA class II immunopeptidomes

ABSTRACT: Major Histocompatibility Complex Class II antigen presentation underlies a wide range of immune responses in health and disease. Although peptide ligand binding affinity has been the major focus for explaining and predicting class II antigens, we know that the levels and activities of accessory molecules, HLA-DM (DM) and HLA-DO (DO) can have strong effects on peptide repertoires. However, the extent to which these antagonistic proteins’ levels relative to one another shape the identities and properties of peptides selected for presentation remains unclear. Hence, after creating cell line panel with varying DO:DM ratios, of we set out to measure the effects these ratios can have on peptide presentation. Using a combined immunopeptidomic and proteomic discovery strategy, we profiled ligandome differences across this panel. By surveying over 10,000 unique HLA-DR4-presented peptides, we found marked increases in repertoire diversity and altered physical properties of presented peptides that corresponded with increasing DO:DM ratios.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Leukocyte

DISEASE(S): Lymphoblastic Lymphoma

SUBMITTER: Niclas Olsson

LAB HEAD: Joshua E. Elias

PROVIDER: PXD024392 | Pride | 2023-10-24

REPOSITORIES: Pride

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Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.

Olsson Niclas N Jiang Wei W Adler Lital N LN Mellins Elizabeth D ED Elias Joshua E JE

Molecular & cellular proteomics : MCP 20220125 3

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. ...[more]

PMID: 35085787

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