ArticleThe Journal of experimental medicine2000
Cytotoxic T lymphocyte epitopes of HIV-1 Nef: Generation of multiple definitive major histocompatibility complex class I ligands by proteasomes.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 77 citations in OpenAlex.
- Long-term specific immune responses induced in humans by a human immunodeficiency virus type 1 lipopeptide vaccine: characterization of CD8+-T-cell epitopes recognized.Journal of virology · 2003Trial
- Isolation of Proteasome-Trapped Peptides (PTPs) for Degradome Analysis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Cross Talk between Radiation and Immunotherapy: The Twain Shall Meet.Radiation research · 2018Review
- Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays.Scientific reports · 2016Article
- Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape.PLoS pathogens · 2015Article
- The immunoproteasome and viral infection: a complex regulator of inflammation.Frontiers in microbiology · 2015Review
- A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice.European journal of immunology · 2014Article
- The VHSE-based prediction of proteasomal cleavage sites.PloS one · 2013Article
- Cell type-specific proteasomal processing of HIV-1 Gag-p24 results in an altered epitope repertoire.Journal of virology · 2011Article
- Recognition of a subregion of human proinsulin by class I-restricted T cells in type 1 diabetic patients.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.Journal of virology · 2004Article
- Discriminating self from nonself with short peptides from large proteomes.Immunogenetics · 2004Article
- Differential proteasomal processing of hydrophobic and hydrophilic protein regions: contribution to cytotoxic T lymphocyte epitope clustering in HIV-1-Nef.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Study of antigen-processing steps reveals preferences explaining differential biological outcomes of two HLA-A2-restricted immunodominant epitopes from human immunodeficiency virus type 1.Journal of virology · 2002Article
- Link between organ-specific antigen processing by 20S proteasomes and CD8(+) T cell-mediated autoimmunity.The Journal of experimental medicine · 2002Article
- 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide.The EMBO journal · 2001Article
- Efficient identification of novel HLA-A(*)0201-presented cytotoxic T lymphocyte epitopes in the widely expressed tumor antigen PRAME by proteasome-mediated digestion analysis.The Journal of experimental medicine · 2001Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH(2) termini are cleaved by aminopeptidases? We determined five naturally processed MHC class I ligands derived from HIV-1 Nef. Unexpectedly, the five ligands correspond to only three cytotoxic T lymphocyte (CTL) epitopes, two of which occur in two COOH-terminal length variants. Parallel analyses of proteasomal digests of a Nef fragment encompassing the epitopes revealed that all five ligands are direct products of proteasomes. Moreover, in four of the five ligands, the NH(2) termini correspond to major proteasome cleavage sites, and putative NH(2)-terminally extended precursor fragments were detected for only one of the five ligands. All ligands are transported by the transporter associated with antigen processing (TAP). The combined results from these five ligands provide strong evidence that many definitive MHC class I ligands are precisely cleaved at both ends by proteasomes. Additional evidence supporting this conclusion is discussed, along with contrasting results of others who propose a strong role for NH(2)-terminal trimming with direct proteasomal epitope generation being a rare event.
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