Title
The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Pathology
Publication Date
2003-03-22
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Most antigenic peptides presented on MHC class I molecules are generated by proteasomes during protein breakdown. It is unknown whether these peptides are protected from destruction by cytosolic peptidases. In cytosolic extracts, most antigenic peptides are degraded by the metalloendopeptidase, thimet oligopeptidase (TOP). We therefore examined whether TOP destroys antigenic peptides in vivo. When TOP was overexpressed in cells, class I presentation of antigenic peptides was reduced. In contrast, TOP overexpression didn't reduce presentation of peptides generated in the endoplasmic reticulum or endosomes. Conversely, preventing TOP expression with siRNA enhanced presentation of antigenic peptides. TOP therefore plays an important role in vivo in degrading peptides released by proteasomes and is a significant factor limiting the extent of antigen presentation.
DOI of Published Version
10.1016/S1074-7613(03)00058-X
Source
Immunity. 2003 Mar;18(3):429-40.
Journal/Book/Conference Title
Immunity
Related Resources
PubMed ID
12648459
Repository Citation
York IA, Mo AX, Lemerise K, Zeng W, Shen Y, Abraham CR, Saric T, Goldberg AL, Rock KL. (2003). The cytosolic endopeptidase, thimet oligopeptidase, destroys antigenic peptides and limits the extent of MHC class I antigen presentation. GSBS Student Publications. https://doi.org/10.1016/S1074-7613(03)00058-X. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/759