Modulation of the Antigenic Peptide Transporter TAP by Recombinant Antibodies Binding to the Last Five Residues of TAP1

Plewnia, Gabriele; Schulze, Katrin; Hunte, Carola; Tampé, Robert; Koch, Joachim

doi:10.1016/j.jmb.2007.02.102

Cited by 19 publications

(9 citation statements)

References 48 publications

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“…Peptide Arrays-Peptide arrays of human BAG-6 (P46379-1; peptides of 18 amino acids offset by one amino acid) were synthesized by Fmoc (N-(9-fluorenyl)methoxycarbonyl) chemistry at activated PEG spacers on cellulose membranes by automated parallel peptide synthesis on a MultiPep RS instrument (Intavis) and used for binding experiments as described previously (19,20). After saturation of unspecific binding sites, peptide membranes were probed with soluble human NKp30-IgG1-Fc fusion proteins (17).…”

Section: Methodsmentioning

confidence: 99%

A Soluble Fragment of the Tumor Antigen BCL2-associated Athanogene 6 (BAG-6) Is Essential and Sufficient for Inhibition of NKp30 Receptor-dependent Cytotoxicity of Natural Killer Cells

Binici

Hartmann

Herrmann

et al. 2013

Journal of Biological Chemistry

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Background: Cellular ligands of the activating natural killer (NK) cell receptor NKp30 are poorly characterized. Results: The identified domain of the cellular ligand BCL2-associated athanogene 6 (BAG-6) is essential and sufficient to bind NKp30 and inhibits NK cell function. Conclusion:The BAG-6 domain from amino acid 686 to 936 is an important element of BAG-6-dependent tumor immune escape. Significance: This study gives the first molecular insights into BAG-6-mediated inhibition of NKp30-dependent NK cell cytotoxicity.

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Section: Methodsmentioning

confidence: 99%

A Soluble Fragment of the Tumor Antigen BCL2-associated Athanogene 6 (BAG-6) Is Essential and Sufficient for Inhibition of NKp30 Receptor-dependent Cytotoxicity of Natural Killer Cells

Binici

Hartmann

Herrmann

et al. 2013

Journal of Biological Chemistry

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“…Antibodies-For immunoblotting and immunoprecipitation, the TAP1 (monoclonal antibody 148.3) and TAP2 (monoclonal antibody 435.3) (31)(32)(33), as well as the polyclonal affinity-purified TAPL-specific (34) and GFP-specific (Dianova) antibodies were used. For detection of UL49.5, two polyclonal rabbit sera were used recognizing N-terminal (H11) and C-terminal epitopes (H19) of UL49.5, respectively (26).…”

Section: Methodsmentioning

confidence: 99%

Signaling of a Varicelloviral Factor across the Endoplasmic Reticulum Membrane Induces Destruction of the Peptide-loading Complex and Immune Evasion

Loch

Klauschies

Schölz

et al. 2008

Journal of Biological Chemistry

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Cytotoxic T lymphocytes eliminate infected cells upon surface display of antigenic peptides on major histocompatibility complex I molecules. To promote immune evasion, UL49.5 of several varicelloviruses interferes with the pathway of major histocompatibility complex I antigen processing. However, the inhibition mechanism has not been elucidated yet. Within the macromolecular peptide-loading complex we identified the transporter associated with antigen processing (TAP1 and TAP2) as the prime target of UL49.5. Moreover, we determined the active oligomeric state and crucial elements of the viral factor. Remarkably, the last two residues of the cytosolic tail of UL49.5 are essential for endoplasmic reticulum (ER)-associated proteasomal degradation of TAP. However, this process strictly requires additional signaling of an upstream regulatory element in the ER lumenal domain of UL49.5. Within this new immune evasion mechanism, we show for the first time that additive elements of a small viral factor and their signaling across the ER membrane are essential for targeted degradation of a multi-subunit membrane complex.

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“…48), anti-GFP (49), anti-huTAP1 mAb 148.3 (50,51), anti-huTAP2 mAb 435.3 (52) (provided by P. van Endert, Faculté de Médecine René Descartes, Paris, France), goat anti-rat TAP1 M18 (Santa Cruz Biotechnology; used for Western blotting), rabbit anti-rat TAP1 D90 (53) (used for immunoprecipitation), anti-rat TAP2 mAb Mac394 (54) (used for Western blotting), sheep anti-rat TAP2 S635 (provided by S. Powis, Bute Medical School,(Serotec), anti-MHC class II L243-PE (BD Pharmingen), and anti-NGFRbiotin (BD Pharmingen) were used. For detection of UL49.5, a rabbit polyclonal anti-serum (H11) was raised using a synthetic peptide derived from the N-terminal domain of BHV-1 UL49.5 as an Ag (56).…”

Section: Antibodiesmentioning

confidence: 99%

The Varicellovirus UL49.5 Protein Blocks the Transporter Associated with Antigen Processing (TAP) by Inhibiting Essential Conformational Transitions in the 6+6 Transmembrane TAP Core Complex

Verweij

Koppers-Lalić

Loch

et al. 2008

The Journal of Immunology

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TAP translocates virus-derived peptides from the cytosol into the endoplasmic reticulum, where the peptides are loaded onto MHC class I molecules. This process is crucial for the detection of virus-infected cells by CTL that recognize the MHC class I-peptide complexes at the cell surface. The varicellovirus bovine herpesvirus 1 encodes a protein, UL49.5, that acts as a potent inhibitor of TAP. UL49.5 acts in two ways, as follows: 1) by blocking conformational changes of TAP required for the translocation of peptides into the endoplasmic reticulum, and 2) by targeting TAP1 and TAP2 for proteasomal degradation. At present, it is unknown whether UL49.5 interacts with TAP1, TAP2, or both. The contribution of other members of the peptide-loading complex has not been established. Using TAP-deficient cells reconstituted with wild-type and recombinant forms of TAP1 and TAP2, TAP was defined as the prime target of UL49.5 within the peptide-loading complex. The presence of TAP1 and TAP2 was required for efficient interaction with UL49.5. Using deletion mutants of TAP1 and TAP2, the 6+6 transmembrane core complex of TAP was shown to be sufficient for UL49.5 to interact with TAP and block its function. However, UL49.5-induced inhibition of peptide transport was most efficient in cells expressing full-length TAP1 and TAP2. Inhibition of TAP by UL49.5 appeared to be independent of the presence of other peptide-loading complex components, including tapasin. These results demonstrate that UL49.5 acts directly on the 6+6 transmembrane TAP core complex of TAP by blocking essential conformational transitions required for peptide transport.

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Modulation of the Antigenic Peptide Transporter TAP by Recombinant Antibodies Binding to the Last Five Residues of TAP1

Cited by 19 publications

References 48 publications

A Soluble Fragment of the Tumor Antigen BCL2-associated Athanogene 6 (BAG-6) Is Essential and Sufficient for Inhibition of NKp30 Receptor-dependent Cytotoxicity of Natural Killer Cells

A Soluble Fragment of the Tumor Antigen BCL2-associated Athanogene 6 (BAG-6) Is Essential and Sufficient for Inhibition of NKp30 Receptor-dependent Cytotoxicity of Natural Killer Cells

Signaling of a Varicelloviral Factor across the Endoplasmic Reticulum Membrane Induces Destruction of the Peptide-loading Complex and Immune Evasion

The Varicellovirus UL49.5 Protein Blocks the Transporter Associated with Antigen Processing (TAP) by Inhibiting Essential Conformational Transitions in the 6+6 Transmembrane TAP Core Complex

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