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Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57

Nature Immunology volume 7, pages 93–102 (2006)Cite this article

Abstract

The thiol-oxidoreductase ERp57 is an integral component of the peptide-loading complex of the major histocompatibility complex (MHC) class I pathway, but its function is unknown. To investigate its function in antigen presentation, we generated ERp57-deficient mice. Death in utero caused by ubiquitous ERp57 deletion was prevented by specific deletion in the B cell compartment. We demonstrate that ERp57 was central for recruitment of MHC class I molecules into the loading complex. In ERp57-deficient cells, we found short-lived interaction of MHC class I molecules with the loading complex. Thus, in the steady state, very few MHC class I molecules were present in the loading complex. Surface H-2Kb–peptide expression and stability were reduced, and presentation of a model antigen was decreased. Our results indicate that ERp57 does not influence the redox state of MHC class I molecules but is an essential structural component required for stable assembly of the peptide-loading complex.

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Figure 1: Generation of tissue-specific ERp57-deficient mice.
Figure 2: ERp57 increases the expression of MHC class I molecules.
Figure 3: ERp57 mediates the recruitment of MHC class I and calreticulin into the peptide-loading complex.
Figure 4: Redox state of MHC class I molecules in the absence of ERp57.
Figure 5: H-2Kb molecules mature faster in the absence of ERp57 but are suboptimally loaded.
Figure 6: Antigen-specific CD8+ T cell activation by ERp57-deficient APCs.

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Acknowledgements

We thank G. Küblbek, S. Schmidt, M. Wühl and N. Bulbuc for technical assistance; T. Oelert for critical reading of the manuscript; M. Molinari (Institute for Research in Biomedicine, Bellinzona, Switzerland) and T. Dick for discussions; and T. Hansen and N. Myers (Washington University School of Medicine, St. Louis, Missouri) for anti-tapasin rabbit serum. Supported by European Union projects MICROBAN (MRTN-CT-504227 to G.J.H.) and NoE-MUGENE (LSHG-CT-2005-005203 to G.J.H.)

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Author notes

  1. Satoshi Tanaka

    Present address: Department of Pathology, Sapporo City General Hospital, 060-8604, Sapporo, Japan

  2. Natalio Garbi and Satoshi Tanaka: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany

    Natalio Garbi, Satoshi Tanaka, Frank Momburg & Günter J Hämmerling

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  1. Natalio Garbi
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Correspondence to Günter J Hämmerling.

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Supplementary Fig. 1

ERp57 increases stability of H-2Kb–peptide complexes. (PDF 47 kb)

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Garbi, N., Tanaka, S., Momburg, F. et al. Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57. Nat Immunol 7, 93–102 (2006). https://doi.org/10.1038/ni1288

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