PCPS: A Web Server to Predict Proteasomal Cleavage Sites

Gómez-Perosanz, Marta; Ras-Carmona, Alvaro; Reche, Pedro A.

doi:10.1007/978-1-0716-0389-5_23

Cited by 20 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 ). Accordingly, in silico analysis of the INS-DRiP sequence on the Proteasome Cleavage Prediction Server (PCPS) [ 28 ] shows that the INS-DRiP 1–9 (MLYQHLLPL) 9-mer has a higher propensity to be processed by the immunoproteasome complex than by the constitutive proteasome. In addition, the localisation of trypsin digestion sites outside the 9-mer epitope region suggests that the β2i subunit may be involved in the processing of the INS-DRiP polypeptide but should not destroy the MLYQHLLPL epitope, meaning that its integrity is maintained.…”

Section: Resultsmentioning

confidence: 99%

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity

et al. 2023

View full text Add to dashboard Cite

Aims/hypothesis The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNɣ) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells. Methods Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome. Specific inhibition of the immunoproteasome catalytic subunits was achieved using siRNA, and antigenic peptide presentation at the cell surface of the human beta cell line EndoC-βH1 was monitored using peptide-specific CD8 T cells. Results We found that IFNγ induces the expression of the PSMB10 transcript encoding the β2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells. Moreover, we showed that PSMB10 is upregulated in a beta cell subset that is preferentially destroyed in the pancreases of individuals with type 1 diabetes. Conclusions/interpretation Our data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes. Data availability The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316). Graphical Abstract

show abstract

Section: Resultsmentioning

confidence: 99%

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity

et al. 2023

View full text Add to dashboard Cite

show abstract

“…All epitopes for MHC I were found to have 100% proteasomal processing (Table 1). This is essential since the proteasome is responsible for the proteolytic degradation and MHC I presentation [33]. Epitopes RVRYYHQL, LWRNAFLAGAVPVVL, and RYFRWRRSFAVHITS were discarded because their interaction sites did not coincide with the speci c MHC pocket [34].…”

Section: Fut4-derived T-cell Epitopes Have Mhci/ii a Nitymentioning

confidence: 99%

Non-cytotoxic carbon nanotubes bioconjugated with fucosyltransferase 4-derived peptides modulate macrophage polarization in vitro

Guzmán-Mendoza

Sánchez‐Ramírez

Cigarroa-Mayorga

et al. 2023

Preprint

View full text Add to dashboard Cite

In recent years, nanotechnology has had an important development in nanoparticle-based therapies. Carbon nanotubes (CNTs) are among the most valuable nanoparticles, given their physicochemical properties and functionalization possibilities; therefore, they are proposed as peptide carriers in immunotherapies. Immunotherapy has been explored as a promising therapy in ovarian cancer (OvCa), and it has been reported that macrophage polarization into M1 and M2 phenotypes plays a pivotal role in OvCa initiation, progression, and metastasis, providing therapeutic targets for macrophage-targeted treatment. In this work, we explored the initial stages for the design of CNTs-based immunotherapy for ovarian cancer (OvCa) using fucosyltransferase-4-derived T cell epitopes conjugated with CNTs (f-CNTs). Their cytotoxicity and biological interactions were analyzed in macrophages (J774A.1) and human ovarian cancer cells (SKOV-3). Here we showed that f-CNTs do not show cytotoxicity signs in concentrations < 6 µg/mL; additionally, they induced morphological changes and activation in macrophages, time-dependent uptake in lysosomes, production of M1-like cytokines, upregulation of CD80, CD86, and MHC II, and downregulation of ARG-1. In conclusion, f-CNTs exhibited biocompatibility in both cell lines and displayed M1-like polarization in macrophages, allowing us to propose them as a peptide carrier system for macrophage activation and polarization for being explored in ovarian cancer immunotherapies.

show abstract

“…A literature search and browser query were performed to identify currently available tools for proteasomal cleavage prediction (search terms included "cleavage prediction", "proteasomal prediction", "cleavage prediction tool", and "proteasomal cleavage prediction"). Through this search, six tools were identified including: NetChop 3.1 10 , the Proteasomal Cleavage Prediction Server (PCPS) 64 , PCleavage 65 , MAPPP 66 , PAProC 67 , and the random forest-based model described in Li et al (2012). NetChop version 3.1 was downloaded (http://www.cbs.dtu.dk/services/NetChop/) and installed as a command line tool on a Linux server running CentOS 7.7.1908.…”

Section: Comparison Of Cleavage Prediction Toolsmentioning

confidence: 99%

“…Eight proteasomal cleavage tools are shown (columns) along with their corresponding features (rows). Specific tools are as follows: pepsickle (presented here), NetChop 3.1 10 , the Proteasomal Cleavage Prediction Server (PCPS) 64 , PCleavage 65 , MAPPP 66 , PAProC 67 , and the random forest-based model described in Li et al 68 Check marks (green) represent available features for each tool while X's (red) represent unavailable features. Warning signs (yellow) represent missing information, or features that are mentioned but not currently available.…”

Section: Figure 2 Comparison Matrix Of Available Proteasomal Cleavage Tools and Their Featuresmentioning

confidence: 99%

Pepsickle rapidly and accurately predicts proteasomal cleavage sites for improved neoantigen identification

Weeder

Wood

et al. 2021

Preprint

View full text Add to dashboard Cite

Proteasomal cleavage is a key component in protein turnover, as well as antigen presentation and subsequent immune response. Herein we present pepsickle, an open-source tool for proteasomal cleavage prediction with better in vivo prediction performance (AUC) and computational speed than current models available in the field, and with the ability to predict sites based on both constitutive and immunoproteasome profiles. Post-hoc filtering of predicted patient neoepitopes using pepsickle significantly enriches for immune-responsive epitopes and may represent a significant opportunity to improve current epitope prediction and vaccine development pipelines.

show abstract

PCPS: A Web Server to Predict Proteasomal Cleavage Sites

Cited by 20 publications

References 19 publications

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity

Non-cytotoxic carbon nanotubes bioconjugated with fucosyltransferase 4-derived peptides modulate macrophage polarization in vitro

Pepsickle rapidly and accurately predicts proteasomal cleavage sites for improved neoantigen identification

Contact Info

Product

Resources

About