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HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation.

ABSTRACT: Peptide loading of class II MHC molecules in endosomal compartments is regulated by HLA-DM. HLA-DO modulates HLA-DM function, with consequences for the spectrum of MHC-bound epitopes presented at the cell surface for interaction with T cells. Here, we summarize and discuss recent progress in investigating the molecular mechanisms of action of HLA-DM and HLA-DO and in understanding their roles in immune responses. Key findings are the long-awaited structures of HLA-DM in complex with its class II substrate and with HLA-DO, and observation of a novel phenotype--autoimmunity combined with immunodeficiency--in mice lacking HLA-DO. We also highlight several areas where gaps persist in our knowledge about this pair of proteins and their molecular biology and immunobiology.

SUBMITTER: Mellins ED

PROVIDER: S-EPMC3944065 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation.

Mellins Elizabeth D ED Stern Lawrence J LJ

Current opinion in immunology 20131208

Peptide loading of class II MHC molecules in endosomal compartments is regulated by HLA-DM. HLA-DO modulates HLA-DM function, with consequences for the spectrum of MHC-bound epitopes presented at the cell surface for interaction with T cells. Here, we summarize and discuss recent progress in investigating the molecular mechanisms of action of HLA-DM and HLA-DO and in understanding their roles in immune responses. Key findings are the long-awaited structures of HLA-DM in complex with its class II ...[more]

PMID: 24463216

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