Deleterious knock-outs in the HLA class I antigen processing and presentation machinery induce distinct changes in the immunopeptidome DOI Creative Commons

Ilja E. Shapiro,

Clélia Maschke,

Justine Michaux

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100951 - 100951

Published: March 1, 2025

The human leukocyte antigen (HLA) processing and presentation machinery (APPM) is altered in various diseases response to drug treatments. Defects the may change levels or alter repertoire of presented peptides, globally an HLA allele restricted manner, with direct implications for adaptive immunity. In this study, we investigated immunopeptidome landscape across a panel isogenic HAP1 cell line clones each knock-out single gene encoding key protein APPM, including B2M, TAP1, TAP2, TAPBP, IRF2, PDIA3, ERAP1, GANAB, SPPL3, CANX, CALR. We applied immunopeptidomic proteomic assess successful knock-outs on level, understand how these proteins participate presentation, contextualize expression presentation. validated absence knocked-out respective samples found that knocking-out APPM component leads loss peptide subsets are normally control wild type cells. assessed immunopeptidomes qualitatively quantitatively, considering factors like diversity, length distribution, binding affinity endogenously expressed alleles demonstrated prominent allele-specific alterations several conditions. CALR, TAP1 led significant changes levels. Overall, work represents first systematic analysis individual components, knocked out under controlled conditions, affects peptidome. This approach could facilitate creation predictive tools capable prioritizing HLA-bound peptides likely be when defects occur, such as cancer viral infections.

Language: Английский

Deleterious knock-outs in the HLA class I antigen processing and presentation machinery induce distinct changes in the immunopeptidome DOI Creative Commons

Ilja E. Shapiro,

Clélia Maschke,

Justine Michaux

et al.

Molecular & Cellular Proteomics, Journal Year: 2025, Volume and Issue: unknown, P. 100951 - 100951

Published: March 1, 2025

The human leukocyte antigen (HLA) processing and presentation machinery (APPM) is altered in various diseases response to drug treatments. Defects the may change levels or alter repertoire of presented peptides, globally an HLA allele restricted manner, with direct implications for adaptive immunity. In this study, we investigated immunopeptidome landscape across a panel isogenic HAP1 cell line clones each knock-out single gene encoding key protein APPM, including B2M, TAP1, TAP2, TAPBP, IRF2, PDIA3, ERAP1, GANAB, SPPL3, CANX, CALR. We applied immunopeptidomic proteomic assess successful knock-outs on level, understand how these proteins participate presentation, contextualize expression presentation. validated absence knocked-out respective samples found that knocking-out APPM component leads loss peptide subsets are normally control wild type cells. assessed immunopeptidomes qualitatively quantitatively, considering factors like diversity, length distribution, binding affinity endogenously expressed alleles demonstrated prominent allele-specific alterations several conditions. CALR, TAP1 led significant changes levels. Overall, work represents first systematic analysis individual components, knocked out under controlled conditions, affects peptidome. This approach could facilitate creation predictive tools capable prioritizing HLA-bound peptides likely be when defects occur, such as cancer viral infections.

Language: Английский

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