The effect of interferons on presentation of defective ribosome products as HLA peptides

ABSTRACT: The class I major histocompatibility complex (MHC) bound peptides, produced from immature proteins that are degraded rapidly are called defective ribosome products (DRiPs). Such DRiPs are possibly involved with early alerting of the immune system about impeding infections, thus bringing about faster killing of infected cells before the viruses replicate. Interferons are a major group of cytokines, produced in response to viral infection. The interferons modulate the cellular metabolism and gene expression patterns and increase the expression and cell-surface presentation of the MHC molecules, helping this way coping with the viral infection. In this study, we evaluated whether the interferons also induce rapid degradation of cellular or viral proteins and produce DRiPs MHC-bound peptides to help the alert of the immune system. Cultured human breast cancer cells were treated with interferons and the cells were transferred to growth media containing heavy stable isotope labeled amino acids (dynamic-SILAC)in several time points a few hours after the interferons’ treatment. The rates of synthesis, degradation, and production of the cellular protein and their degradation products, the MHC peptides, were followed by LC-MS/MS analyses. Detection of large numbers of MHC peptides that incorporate the heavy amino acids into them, faster than their source proteins, indicated to us that not only DRiP-peptides are rather abundant among the MHC peptidome, but that the interferons increase significantly the presentation of DRiP-peptides. Importantly, much of this DRiPome derive from multi-subunit complexes, including the proteasomes and ribosomes, while the degradation of the standard protostome give rise to the immunoproteasome, which is thought to produce peptides that enhance the immune-response; the degradation of the ribosome subunits may aid in reducing the synthesis of viral infection

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Breast Cancer

SUBMITTER: Dganit Melamed Kadosh  

LAB HEAD: Arie Admon

PROVIDER: PXD022633 | Pride | 2021-06-09

REPOSITORIES: Pride