The Effect of Interferons on Presentation of Defective Ribosomal Products as HLA Peptides.

A subset of class I major histocompatibility complex (MHC)-bound peptides is produced from immature proteins that are rapidly degraded after synthesis. These defective ribosomal products (DRiPs) have been implicated in early alert of the immune system about impending infections. Interferons are important cytokines, produced in response to viral infection, that modulate cellular metabolism and gene expression patterns, increase the presentation of MHC molecules, and induce rapid degradation of proteins and cell-surface presentation of their derived MHC peptides, thereby contributing to the battle against pathogen infections.

Cell Surface MHC Class I Expression Is Limited by the Availability of Peptide-Receptive "Empty" Molecules Rather than by the Supply of Peptide Ligands.

While antigen processing and presentation (APP) by the major histocompatibility complex class I (MHC-I) molecules have been extensively studied, a question arises as to whether the level of MHC-I expression is limited by the supply of peptide-receptive (empty) MHC molecules, or by the availability of peptide ligands for loading. To this end, the effect of interferons (IFNs) on the MHC peptidomes of human breast cancer cells (MCF-7) were evaluated. Although all four HLA allotypes of the MCF-7 cells (HLA-A*02:01, B*18, B*44, and C*5) present peptides of similar lengths and C-termini, which should be processed similarly by the proteasome and by the APP chaperones, the IFNs induced differential modulation of the HLA-A, B, and C peptidomes.