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Osterloh, P.* ; Linkemann, K. ; Tenzer, S.* ; Rammensee, H.-G.* ; Radsak, M.P.* ; Busch, D.H. ; Schild, H.*

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

Proc. Natl. Acad. Sci. U.S.A. 103, 5042-5047 (2006)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords T cell repertoire; selection; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; THYMOCYTE-POSITIVE SELECTION; I-PRESENTED PEPTIDES; QUANTITATIVE-ANALYSIS; PROTEIN-DEGRADATION; 20S PROTEASOME; MHC; IMMUNOPROTEASOMES; GENERATION; EPITOPE
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 103, Issue: 13, Pages: 5042-5047 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)