The nature and extent of contributions by defective ribosome products to the HLA peptidome

Abstract

Significance Rapid degradation of newly synthesized proteins, followed by presentation of the resulting peptides by the MHC molecules, serves as an early alert for the immune system during pathogen infection. This study defines the relative contribution to the MHC peptidome of defective ribosome products (DRiPs), which are newly synthesized and rapidly degraded proteins, vs. mature proteins, degraded at the end of their functional lifetimes (retirees). The rates of synthesis of the individual MHC peptides and their source proteins were followed using stable isotope labeling and quantitative proteomics and peptidomics analyses. We conclude that DRiPs are a significant source of MHC peptides. Many of these DRiPs are misassembled surplus subunits of protein complexes and therefore are degraded soon after synthesis.

Naturally Processed Non-canonical HLA-A*02:01 Presented Peptides

“…It is important to note that in large scale proteomics experiments a certain false discovery rate is acceptable. For HLA-presented peptides 5% is accepted as the false discovery rate (8,29). Therefore, it cannot be excluded that a few peptides might have been incorrectly assigned, but the large majority will have been correctly assigned.…”

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

“…Shield-1-sensitive fusion proteins offered unparalleled posttranslational control over a particular substrate; however, they are model proteins, and it is unknown whether Chlamydia infections happen to target elements of these fusion proteins or DRiPs in general. While in vitro experiments have demonstrated that cells of hematopoietic origin, such as dendritic cells and macrophages (42,43), can be infected with different Chlamydia species, epithelial cells are the primary target of infections in vivo and antigenic peptides derived from DRiPs are present in different amounts depending on the cell type (44). However, the phenomenon is not limited to JY cells, since an epithelial cell line transiently transfected with SCRAP-SVG also increased DRiP presentation, while stable protein accumulation was diminished (Fig.…”

Analysis of Major Histocompatibility Complex-Bound HIV Peptides Identified from Various Cell Types Reveals Common Nested Peptides and Novel T Cell Responses

“…The presentation of vaccinia virus-derived peptides over 12 h (15) and the presentation of both modified vaccinia Ankara (MVA) peptides and HIV peptides from Jurkat cells infected with MVA expressing HIV protein fragments followed during 6 h (16) showed variations in epitope presentation over time. While peptide presentation was linked to protein expression (15,16), defective translation products (defective ribosomal products [DRiPs]) may also contribute to various extents to the pool of MHC-I peptides displayed by cells (35)(36)(37).…”