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Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer

Nature Immunology volume 8, pages 873–881 (2007)Cite this article

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Abstract

Major histocompatibility complex (MHC) class I glycoproteins bind peptides in the endoplasmic reticulum after incorporation into the peptide-loading complex, whose core is the transporter associated with antigen processing. Other components are the chaperone calreticulin, the thiol oxidoreductase ERp57, and tapasin. Tapasin and ERp57 have been shown to exist in the peptide-loading complex as a disulfide-linked heterodimer. Here, using a cell-free system, we demonstrate that although recombinant tapasin was ineffective in recruiting MHC class I molecules and facilitating peptide binding, recombinant tapasin-ERp57 conjugates accomplished both of those functions and also 'edited' the repertoire of bound peptides to maximize their affinity. Thus, the tapasin-ERp57 conjugate is the functional unit of the peptide-loading complex that generates MHC class I molecules with stably associated peptides.

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Figure 1: Expression and analysis of recombinant tapasin-ERp57 conjugates.
Figure 2: Assay for PLC subcomplex assembly and function.
Figure 3: The recombinant conjugate interacts with newly synthesized MHC class I molecules.
Figure 4: The conjugate stabilizes MHC class I molecules and facilitates peptide loading.
Figure 5: A peptide-editing function for the tapasin-ERp57 conjugate.

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Change history

  • 13 July 2007

    In the version of this article initially published online, the right side of Figure 1c was cut off. The error has been corrected for all versions of the article.

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Acknowledgements

We thank D. Peaper for discussions and critical review of the manuscript; S. Mitchell, R. Teel and A. Little for technical assistance; and N. Dometios for aid in preparing this manuscript. Supported by the Howard Hughes Medical Institute.

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  1. Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, 06520-8011, Connecticut, USA

    Pamela A Wearsch & Peter Cresswell

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P.A.W. designed and implemented all experiments; P.A.W. and P.C. wrote the paper.

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Correspondence to Peter Cresswell.

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Wearsch, P., Cresswell, P. Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer. Nat Immunol 8, 873–881 (2007). https://doi.org/10.1038/ni1485

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