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Mediation by HLA-DM of dissociation of peptides from HLA-DR

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Abstract

HUMAN leukocyte antigen (HLA)-DM is an unconventional major histocompatibility complex (MHC) class II heterodimer that is important for B-cell-mediated antigen processing and presentation to MHC class II-restricted T cells1–12. HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region1, and shares some homology with MHC class I and class II proteins2,3. Here we define the biochemical role of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purified from culture supernatants of insect cell transformants. At pH 5.0, they induce the dissociation of a subset of peptides bound to HLA-DR, including a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced binding of exogenous peptides.

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Author notes

  1. Dennis M. Zaller: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Autoimmune Disease Research, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Victor S. Sloan, Gene Porter & Maureen Gammon

  2. Department of Molecular Design and Diversity, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Patricia Cameron

  3. Departments of Molecular Immunology, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    Dennis M. Zaller

  4. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, 19104, USA

    Miguel Amaya & Elizabeth Mellins

Authors
  1. Victor S. Sloan
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  2. Patricia Cameron
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  3. Gene Porter
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  4. Maureen Gammon
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  5. Miguel Amaya
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  6. Elizabeth Mellins
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  7. Dennis M. Zaller
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Sloan, V., Cameron, P., Porter, G. et al. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375, 802–806 (1995). https://doi.org/10.1038/375802a0

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  • DOI: https://doi.org/10.1038/375802a0

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