ArticleMolecular & cellular proteomics : MCP2012
The origin of proteasome-inhibitor resistant HLA class I peptidomes: a study with HLA-A*68:01.
Article in Molecular & cellular proteomics : MCP, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise.Proteomics · 2021Review
- The Effect of Interferons on Presentation of Defective Ribosomal Products as HLA Peptides.Molecular & cellular proteomics : MCP · 2021Article
- Endoplasmic reticulum aminopeptidase 1 and rheumatic disease: functional variation.Current opinion in rheumatology · 2015Review
- Peptide handling by HLA-B27 subtypes influences their biological behavior, association with ankylosing spondylitis and susceptibility to endoplasmic reticulum aminopeptidase 1 (ERAP1).Molecular & cellular proteomics : MCP · 2014Article
- The nature and extent of contributions by defective ribosome products to the HLA peptidome.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Translating DRiPs: MHC class I immunosurveillance of pathogens and tumors.Journal of leukocyte biology · 2014Review
- Proteasome inhibitors alter levels of intracellular peptides in HEK293T and SH-SY5Y cells.PloS one · 2014Article
- Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon endogenous processing of bacterial proteins suggest a role of molecular mimicry in reactive arthritis.The Journal of biological chemistry · 2013Article
- The effect of proteasome inhibition on the generation of the human leukocyte antigen (HLA) peptidome.Molecular & cellular proteomics : MCP · 2013Article
- Functional interaction of the ankylosing spondylitis-associated endoplasmic reticulum aminopeptidase 1 polymorphism and HLA-B27 in vivo.Molecular & cellular proteomics : MCP · 2012Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Some HLA class I molecules bind a significant fraction of their constitutive peptidomes in the presence of proteasome inhibitors. In this study, A*68:01-bound peptides, and their parental proteins, were characterized through massive mass spectrometry sequencing to refine its binding motif, including the nearly exclusive preference for C-terminal basic residues. Stable isotope tagging was used to distinguish proteasome-inhibitor sensitive and resistant ligands. The latter accounted for less than 20% of the peptidome and, like in HLA-B27, arose predominantly from small and basic proteins. Under the conditions used for proteasome inhibition in vivo, epoxomicin and MG-132 incompletely inhibited the hydrolysis of fluorogenic substrates specific for the tryptic or for both the tryptic and chymotryptic subspecificities, respectively. This incomplete inhibition was also reflected in the cleavage of synthetic peptide precursors of A*68:01 ligands. For these substrates, the inhibition of the proteasome resulted in altered cleavage patterns. However these alterations did not upset the balance between cleavage at peptide bonds resulting in epitope destruction and those leading to their generation. The results indicate that inhibitor-resistant HLA class I ligands are not necessarily produced by non-proteasomal pathways. However, their generation is not simply explained by decreased epitope destruction upon incomplete proteasomal inhibition and may require additional proteolytic steps acting on incompletely processed proteasomal products.
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