Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex (original) (raw)

Nature volume 355, pages 641–644 (1992)Cite this article

Abstract

PRESENTATION of cytoplasmic antigens to class I-restricted cytotoxic T cells implied the existence of a specialized peptide transporter1–3 (reviewed in ref. 4). For most class I heavy chains, association with peptides of the appropriate length is required for stable assembly with β 2-microglobulin5–11. Mutant cells RMA–S (ref. 12) and .174/T2 (refs 13,14) neither assemble stable class I molecules nor present intracellular antigens, and we have suggested that they have lost a function required for the transport of short peptides from the cytosol to the endoplasmic reticulum5–7. The genetic defect in .174 has been localized to a large deletion in the class II region of the major histocompatibility complex6,15,16, within which two genes (RING4 and RING11) have been identified that code for 'ABC' (ATP-binding cassette) transporters15,17–21. We report here that the protein products of these two genes assemble to form a complex. Defects in either protein result in the formation of unstable class I molecules and loss of presentation of intracellular antigens. The molecular defect in a new mutant, BM36.1, is shown to be in the ATP-binding domain of the RING11/PSF2 protein. This is in contrast to the mutant .134 (ref. 15), which lacks the RING4/PSF1 protein.

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK
    Adrian Kelly, Stephen H. Powis, Lesley-Anne Kerr, Ian Mockridge & John Trowsdale
  2. Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU, UK
    Timothy Elliott, Judy Bastin & Alain Townsend
  3. Institut für Experimented Onkologie Und Transplantationsmedizin, Universitätsklinikum Rudolf Virchow, Freie Universität Berlin, Spandauer Damn 130, DW-1000, Berlin, 19, Germany
    Barbara Uchanska-Ziegler & Andreas Ziegler

Authors

  1. Adrian Kelly
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  2. Stephen H. Powis
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  3. Lesley-Anne Kerr
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  4. Ian Mockridge
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  5. Timothy Elliott
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  6. Judy Bastin
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  7. Barbara Uchanska-Ziegler
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  8. Andreas Ziegler
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  9. John Trowsdale
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  10. Alain Townsend
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Kelly, A., Powis, S., Kerr, LA. et al. Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex.Nature 355, 641–644 (1992). https://doi.org/10.1038/355641a0

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