Antigen presentation by the human leukocyte antigen (HLA) on the cell surface is critical for the transduction of the immune signal toward cytotoxic T lymphocytes. DNA damage upregulates HLA class I presentation; however, the mechanism is unclear. Here, we show that DNA-damage-induced HLA (di-HLA) presentation requires an immunoproteasome, PSMB8/9/10, and antigen-transporter, TAP1/2, demonstrating that antigen production is essential. Furthermore, we show that di-HLA presentation requires ATR, AKT, mTORC1, and p70-S6K signaling. Notably, the depletion of CBP20, a factor initiating the pioneer round of translation (PRT) that precedes nonsense-mediated mRNA decay (NMD), abolishes di-HLA presentation, suggesting that di-antigen production requires PRT. RNA-seq analysis demonstrates that DNA damage reduces NMD transcripts in an ATR-dependent manner, consistent with the requirement for ATR in the initiation of PRT/NMD. Finally, bioinformatics analysis identifies that PRT-derived 9-mer peptides bind to HLA and are potentially immunogenic. Therefore, DNA damage signaling produces immunogenic antigens by utilizing the machinery of PRT/NMD.
Pubmed ID: 35594857 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
A software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware providing a set of functions to generate high-resolution Venn and Euler plots. Includes handling for several special cases, including two-case scaling, and extensive customization of plot shape and structure.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsSoftware package for quantifying gene and isoform abundances from single end or paired end RNA Seq data. Accurate transcript quantification from RNA Seq data with or without reference genome. Used for accurate quantification of gene and isoform expression from RNA-Seq data.
View all literature mentionsThis monoclonal targets HLA-A
View all literature mentionsThis monoclonal targets Mouse IgG2b, kappa Isotype Control
View all literature mentionsThis polyclonal targets ZC3H12A
View all literature mentionsThis monoclonal targets TREX1
View all literature mentionsThis polyclonal targets Roquin
View all literature mentionsThis monoclonal targets eIF4E
View all literature mentionsThis polyclonal targets APOBEC3C
View all literature mentionsThis monoclonal targets APOBEC3B
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis monoclonal targets XRCC5
View all literature mentionsThis monoclonal targets CENPF
View all literature mentionsThis polyclonal targets Histone H2A antibody - ChIP Grade
View all literature mentionsThis monoclonal targets cGAS
View all literature mentionsThis monoclonal targets SMG-1 (D42D5) Rabbit mAb
View all literature mentionsThis monoclonal targets RNA Polymerase II
View all literature mentionsThis polyclonal targets POLR2AphosphoS2
View all literature mentionsThis monoclonal targets POLR2AphosphoS5
View all literature mentionsThis monoclonal targets p70 S6 Kinase, phospho (Thr389)
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal targets KAP1 - ChIP Grade
View all literature mentionsThis unknown targets Phospho-KAP-1 (Ser824)
View all literature mentionsThis monoclonal targets ATM (D2E2) Rabbit mAb
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis monoclonal targets Chek1
View all literature mentionsThis monoclonal targets Chk1, phospho (Ser345)
View all literature mentionsThis monoclonal targets ATR
View all literature mentionsThis polyclonal targets Phospho-ATR
View all literature mentionsThis monoclonal targets Human HLA- A, B, C
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis polyclonal targets PSMB9
View all literature mentionsThis monoclonal targets PSMB8
View all literature mentionsCell line WiDr is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RKO is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions