The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire

Basler, Michael; Mundt, Sarah; Gröttrup, Marcus

The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire

Dateien

Basler_2-17hlfyt7hbkt95.pdfGröße: 310.6 KBDownloads: 207

Datum

2018

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

European Journal of Immunology. 2018, 48(3), pp. 419-429. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201747282

Zusammenfassung

Cells of hematopoietic origin express high levels of the immunoproteasome, a cytokine-inducible variant of the proteasome which has been implicated in regulating inflammatory responses and antigen presentation. In the thymus, medullary thymic epithelial cells (mTECs) and cortical thymic epithelial cells (cTECs) do express different proteasome subunits exerting chymotrypsin-like activities suggesting distinct functions in thymic T cell selection. Employing the lymphocytic choriomeningitis virus (LCMV) infection model, we could show that the immunoproteasome subunit LMP7 was absolutely required for the generation of LCMV GP118-125 -specific T cells although the class I mediated presentation of GP118-125 was not dependent on LMP7. Using bone marrow chimeras and adoptive transfer of LMP7-deficient CD8(+) T cells into RAG1-deficient mice we show that LMP7-deficient mice lacked GP118-125 -specific T cell precursors and that LMP7 was required in radioresistant cells - most likely thymic epithelial cells - to enable their selection. Since LMP7 is strongly expressed in negatively selecting mTECs but barely in positively selecting cTECs our data suggest that LMP7 was required to avoid excessive negative selection of GP118-125 -specific T cell precursors. Taken together, this study demonstrates that the immunoproteasome is a crucial factor for filling up holes within the cytotoxic T cell repertoire.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

BASLER, Michael, Sarah MUNDT, Marcus GRÖTTRUP, 2018. The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire. In: European Journal of Immunology. 2018, 48(3), pp. 419-429. ISSN 0014-2980. eISSN 1521-4141. Available under: doi: 10.1002/eji.201747282

BibTex

@article{Basler2018-03immun-40526,
  year={2018},
  doi={10.1002/eji.201747282},
  title={The immunoproteasome subunit LMP7 is required in the murine thymus for filling up a hole in the T cell repertoire},
  number={3},
  volume={48},
  issn={0014-2980},
  journal={European Journal of Immunology},
  pages={419--429},
  author={Basler, Michael and Mundt, Sarah and Gröttrup, Marcus}
}

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