Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex (original) (raw)
- Letter
- Published: 13 February 1992
- Stephen H. Powis1,
- Lesley-Anne Kerr1,
- Ian Mockridge1,
- Timothy Elliott2,
- Judy Bastin2,
- Barbara Uchanska-Ziegler3,
- Andreas Ziegler3,
- John Trowsdale1 &
- …
- Alain Townsend2
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
- Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX, UK
Adrian Kelly, Stephen H. Powis, Lesley-Anne Kerr, Ian Mockridge & John Trowsdale - Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU, UK
Timothy Elliott, Judy Bastin & Alain Townsend - 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
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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
- Received: 30 October 1991
- Accepted: 05 December 1991
- Issue Date: 13 February 1992
- DOI: https://doi.org/10.1038/355641a0