Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation.
Sci Adv
; 9(25): eade7890, 2023 06 23.
Article
in En
| MEDLINE
| ID: mdl-37352349
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 atypical peptides. Our results suggest that generation of MHC class Iâ¢peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antigen Presentation
/
Proteasome Endopeptidase Complex
Language:
En
Journal:
Sci Adv
Year:
2023
Document type:
Article
Affiliation country:
United States