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

Nat Immunol. 2003 Apr;4(4):375-9. doi: 10.1038/ni905. Epub 2003 Feb 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases
  • Anti-Bacterial Agents / pharmacology
  • Antigen Presentation / immunology
  • Cysteine Endopeptidases / metabolism
  • Dendritic Cells / immunology
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Endopeptidases / immunology
  • Endopeptidases / metabolism*
  • Epitopes / biosynthesis*
  • HIV / immunology*
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Multienzyme Complexes / metabolism
  • Oligopeptides / pharmacology
  • Proteasome Endopeptidase Complex
  • RNA, Small Interfering / metabolism


  • Anti-Bacterial Agents
  • Epitopes
  • Histocompatibility Antigens Class I
  • Multienzyme Complexes
  • Oligopeptides
  • RNA, Small Interfering
  • Endopeptidases
  • Aminopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • epoxomicin