Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation.

ABSTRACT: Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypi

SUBMITTER: Mamrosh JL 

PROVIDER: S-EPMC10289651 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature