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Nat Immunol. 2003 Apr;4(4):375-9. Epub 2003 Feb 24.

An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope.

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Institut für Biochemie-Charité, Medical Faculty of the Humboldt-University Berlin, Monbijoustr. 2, 10117 Berlin, Germany.


Most of the peptides presented by major histocompatibility complex (MHC) class I molecules require processing by proteasomes. Tripeptidyl peptidase II (TPPII), an aminopeptidase with endoproteolytic activity, may also have a role in antigen processing. Here, we analyzed the processing and presentation of the immunodominant human immunodeficiency virus epitope HIV-Nef(73-82) in human dendritic cells. We found that inhibition of proteasome activity did not impair Nef(73-82) epitope presentation. In contrast, specific inhibition of TPPII led to a reduction of Nef(73-82) epitope presentation. We propose that TPPII can act in combination with or independent of the proteasome system and can generate epitopes that evade generation by the proteasome-system.

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