Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses

Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5042-7. doi: 10.1073/pnas.0509256103. Epub 2006 Mar 20.


Differences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cpalpha1), is efficiently generated only by immunoproteasomes. Furthermore, OT-1 mice backcrossed onto low molecular mass protein 7 (LMP7)-deficient mice show a 50% reduction of OT-1 cells. This deficiency is also observed after transfer of BM from OT-1 mice in LMP7-deficient mice and can be corrected by the injection of the Cpalpha1 peptide. Interestingly, WT and LMP7-deficient mice mount comparable immune responses to the ovalbumin-derived epitope SIINFEKL. However, their cytotoxic T lymphocytes (CTL) differ in the use of T cell receptor Vbeta genes. CTL derived from WT mice use Vbeta8 or Vbeta5 (the latter is also used by OT-1 cells), whereas SIINFEKL-specific CTL from LMP7-deficient mice are exclusively Vbeta8-positive. Taken together, our experiments provide strong evidence that proteasomal specificity shapes the repertoire of T cells participating in antigen-specific immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Capping Proteins / chemistry
  • Actin Capping Proteins / immunology
  • Amino Acid Sequence
  • Animals
  • Antigens / immunology*
  • Bone Marrow Transplantation / immunology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Ovalbumin / chemistry
  • Ovalbumin / immunology
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Proteasome Endopeptidase Complex / metabolism*
  • Receptors, Antigen, B-Cell / immunology
  • Selection, Genetic
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • Actin Capping Proteins
  • Antigens
  • Multienzyme Complexes
  • Peptide Fragments
  • Receptors, Antigen, B-Cell
  • Ovalbumin
  • LMP7 protein
  • Proteasome Endopeptidase Complex