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Ham-2 corrects the class I antigen-processing defect in RMA-S cells

Nature volume 355, pages 647–649 (1992)Cite this article

Abstract

THE murine major histocompatibility complex (MHC) contains two genes (Ham-1 and Ham-2) that encode members of a super-family of ATP-dependent transport proteins1,2. These genes are believed to mediate the transport of peptide antigen from the cytoplasm into the lumen of the endoplasmic reticulum for binding by MHC class I molecules. Evidence for such a function has come from the rescue of class I surface expression by a cloned copy of the human homologue of Ham-1, PSF-1, in a human cell line that is defective in antigen processing3. A mutant murine cell line, RMA-S, has an identical antigen-processing-defective phenotype4,5. Here we show that expression of a cloned copy of the Ham-2 gene in RMA-S cells results in recovery of the ability to process and present class I-restricted antigens to cytotoxic T lymphocytes, and in partial recovery of class I surface expression. Processing defects for classical (H-2 K and D) and non-classical (Qal and HMT) class I molecules are corrected by Ham-2. These data indicate that both MHC-linked transporter genes are probably required for class I antigen processing, and that the functional transporter in this pathway may consist of a Ham-l/Ham-2 heterodimer.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, 23298–0678, USA

    Michelle Attaya, Coleen K. Martinez & John J. Monaco

  2. Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle, Washington, 98195, USA

    Stephen Jameson & Michael J. Bevan

  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, 75235–9050, USA

    Kirsten Fischer Lindahl

  4. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, 75235–9050, USA

    Carla Aldrich, James Forman & Kirsten Fischer Lindahl

  5. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, 75235–9050, USA

    Kirsten Fischer Lindahl

  6. The Graduate Immunology Program, University of Texas Southwestern Medical Center, Dallas, Texas, 75235–9050, USA

    Evan Hermel

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  1. Michelle Attaya
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Attaya, M., Jameson, S., Martinez, C. et al. Ham-2 corrects the class I antigen-processing defect in RMA-S cells. Nature 355, 647–649 (1992). https://doi.org/10.1038/355647a0

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