γ-Interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes
- 16 September 1993
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 365 (6443), 264-267
- https://doi.org/10.1038/365264a0
Abstract
The presentation of intracellular proteins to the immune system requires their degradation to small peptides that then become associated with major histocompatibility complex (MHC) class I molecules. The generation of these peptides may involve the 20S or 26S proteasome particles, which contain multiple proteolytic activities including distinct sites that preferentially cleave small peptides on the carboxyl side of hydrophobic, basic or acidic residues. Degradation of most cell proteins requires their conjugation to ubiquitin before hydrolysis by the 26S proteasome. This large complex contains the 20S proteasome as its proteolytic core. This ubiquitin-dependent proteolytic pathway is implicated in MHC class I presentation. gamma-Interferon (gamma-IFN), a stimulator of antigen presentation, induces a subclass of proteasomes that contain two MHC-encoded subunits, LMP2 and 7 (refs 5-10). Here we show that gamma-interferon alters the peptidase activities of the 20S and 26S proteasomes without affecting the rates of breakdown of proteins or of ubiquitinated proteins. By enhancing the expression of MHC genes, gamma-IFN increases the proteasomes' capacity to cleave small peptides after hydrophobic and basic residues but reduces cleavage after acidic residues. Moreover, proteasomes of mutants lacking LMP subunits show decreased rates of cleavage after hydrophobic and basic residues. Thus, gamma-IFN and expression of these MHC genes should favour the production by proteasomes of the types of peptides found on MHC class I molecules, which terminate almost exclusively with hydrophobic or basic residues.Keywords
This publication has 29 references indexed in Scilit:
- A molecular model of MHC class-I-restricted antigen processingImmunology Today, 1992
- Proteolysis, proteasomes and antigen presentationNature, 1992
- A controlled breakdown: Antigen processing and the turnover of viral proteinsCell, 1992
- Second proteasome-related gene in the human MHC class II regionNature, 1991
- Homology of proteasome subunits to a major histocompatibility complex-linked LMP geneNature, 1991
- Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complexNature, 1991
- Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexesNature, 1991
- Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporterNature, 1991
- Antigen Recognition by Class I-Restricted T LymphocytesAnnual Review of Immunology, 1989
- Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones.The Journal of Experimental Medicine, 1986