Generation of the vesicular stomatitis virus nucleoprotein cytotoxic T lymphocyte epitope requires proteasome-dependent and -independent proteolytic activities

Stoltze, Lars; Dick, Tobias P.; Deeg, Martin; Pömmerl, Beate; Rammensee, Hans Georg; Schild, Hansjörg

doi:10.1002/(sici)1521-4141(199812)28:12<4029::aid-immu4029>3.0.co;2-n

Cited by 68 publications

(43 citation statements)

References 33 publications

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“…Fourth, the chlamydial peptide, as well as an N-terminally extended precursor are directly produced in vitro by the 20 S proteasome, suggesting that DNA primase (211-222) might be generated in vivo following chlamydial infection. Direct generation of natural HLA-B27 and other MHC class I ligands by the 20 S proteasome in vitro has been repeatedly demonstrated (38,(45)(46)(47)(48), and in vitro peptide generation by the 20 S proteasome has been used to predict natural ligands (26,49). Involvement of the host proteasome in the generation of chlamydial CTL epitopes was recently suggested (50).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Ramos¹,

Álvarez²,

Sesma³

et al. 2002

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Ramos¹,

Álvarez²,

Sesma³

et al. 2002

Journal of Biological Chemistry

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“…The absence of C-terminal excision of CTL epitopes in proteasome-inhibited cells [8][9][10] , together with failure to detect C-terminal trimming activities in the cytosol or ER, has led to the current notion that solely the proteasome liberates the exact C-terminus 1,2 . Cytosolic endopeptidases, however, may also produce peptides with a C-terminus fit for class I binding from protein degradation products lacking such an anchor.…”

Section: Introductionmentioning

confidence: 99%

Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes

et al. 2010

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Cytoxic T lymphocytes (CTLs) recognize peptides presented by HLA class I molecules on the cell surface. The C-terminus of these CTL epitopes is predominantly generated by the proteasome.Here we demonstrate that the cytosolic endopeptidases nardilysin and thimet oligopeptidase (TOP) complemented proteasome activity. Nardilysin and TOP were required, either together or alone, for the generation of a tumor-specific CTL epitope from PRAME, an immunodominant CTL epitope from Epstein-Barr virus, and a clinically important epitope from melanoma-protein MART-1. TOP functioned as C-terminal trimming peptidase in antigen processing and nardilysin contributed to both C-terminal and N-terminal CTL epitope generation. By broadening the antigenic peptide repertoire, nardilysin and TOP strengthen the immune defense against intracellular pathogens and cancer.

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“…A prerequisite for the induction of a CTL response is the generation of peptides from their precursor polypeptides. The major cytosolic protease associated with the generation of antigenic peptides -in particular the C-terminal end of the peptides -is the proteasome [2][3][4][5][6]. After protea-somal cleavage the peptides may be trimmed at the Nterminal end by other peptidases in the cytosol [7].…”

Section: Introductionmentioning

confidence: 99%

An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions

Larsen

Lundegaard

Lamberth³

et al. 2005

Eur. J. Immunol.

281

254

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Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and Cterminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method. The method is available at

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Generation of the vesicular stomatitis virus nucleoprotein cytotoxic T lymphocyte epitope requires proteasome-dependent and -independent proteolytic activities

Cited by 68 publications

References 33 publications

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Molecular Mimicry of an HLA-B27-derived Ligand of Arthritis-linked Subtypes with Chlamydial Proteins

Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes

An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions

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