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Nature Immunology
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Tetraspan microdomains distinct from lipid rafts enrich select peptide–MHC class II complexes

Nature Immunologyvolume 3, pages61–68 (2002)Cite this article

Abstract

Complexes of peptide and major histocompatibility complex (MHC) class II are expressed on the surface of antigen-presenting cells but their molecular organization is unknown. Here we show that subsets of MHC class II molecules localize to membrane microdomains together with tetraspan proteins, the peptide editor HLA-DM and the costimulator CD86. Tetraspan microdomains differ from other membrane areas such as lipid rafts, as they enrich MHC class II molecules carrying a selected set of peptide antigens. Antigen-presenting cells deficient in tetraspan microdomains have a reduced capacity to activate CD4+ T cells. Thus, the organization of uniformly loaded peptide–MHC class II complexes in tetraspan domains may be a very early event that determines both the composition of the immunological synapse and the quality of the subsequent T helper cell response.

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Figure 1: Specific peptide–MHC class II complexes accumulate in CDw78 microdomains.
Figure 2: CDw78 microdomains are distinct from TX-100 insoluble lipid rafts.
Figure 3: Peptide sequence determines segregation of peptide–MHC class II complexes into CDw78 microdomains.
Figure 4: The peptide editor DM is localized in CDw78 microdomains.
Figure 5: CDw78 microdomains of Jutthom B cells comprise A2-DR1 complexes localized in internal compartments and on the cell surface.
Figure 6: Developing DCs up-regulate CDw78 microdomains that contain the costimulatory molecule CD86.
Figure 7: CDw78 microdomains are crucial for T cell activation.

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Acknowledgements

We thank T. Kamradt for the T cell hybridomas; X. D. Nguyen and H. Klüter for the HLA-typed blood samples; D. Roeder for help with mass spectrometry analysis; D. Avila for peptide synthesis: and T. Harder and E. Palmer for helpful discussions. Supported by project A026 of the Czech Ministry of Education (V. H.). The Basel Institute was founded and supported by Hoffman-La Roche, Ltd., Basel.

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Authors and Affiliations

  1. Basel Institute for Immunology, Basel, 4005, Switzerland

    H. Kropshofer, S. Spindeldreher, T. A. Röhn, N. Platania, C. Grygar, N. Daniel & A. B. Vogt

  2. Roche Center for Medical Genomics, Basel, 4070, Switzerland

    H. Kropshofer & A. B. Vogt

  3. German Red Cross, Blood Transfusion Service, Ulm, 89081, Germany

    A. Wölpl

  4. F. Hoffmann-La Roche Ltd., Pharmaceutical Research, Basel, 4070, Switzerland

    H. Langen

  5. Institute of Molecular Genetics, AS CR, Prague, 14220, Czech Republic

    V. Horejsi

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  1. H. Kropshofer

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Correspondence toH. Kropshofer.

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Kropshofer, H., Spindeldreher, S., Röhn, T.et al. Tetraspan microdomains distinct from lipid rafts enrich select peptide–MHC class II complexes.Nat Immunol3, 61–68 (2002). https://doi.org/10.1038/ni750

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