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Sibling rivalry: competition between MHC class II family members inhibits immunity

Nature Structural & Molecular Biology volume 20, pages 7–10 (2013)Cite this article

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Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

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Figure 1: Differential localization of HLA-DM–HLA-DO and HLA-DM complexes in multivesicular endosomes results in the presentation of a diverse repertoire of MHC-bound peptides on the surface of APCs.

Katie Vicari

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Authors and Affiliations

  1. Lisa K. Denzin is at the Child Health Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA.,

    Lisa K. Denzin

  2. Peter Cresswell is at the Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.,

    Peter Cresswell

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  1. Lisa K. Denzin
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  2. Peter Cresswell
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Correspondence to Lisa K. Denzin or Peter Cresswell.

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Denzin, L., Cresswell, P. Sibling rivalry: competition between MHC class II family members inhibits immunity. Nat Struct Mol Biol 20, 7–10 (2013). https://doi.org/10.1038/nsmb.2484

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