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Nat Immunol. 2012 Feb 5;13(3):237-45. doi: 10.1038/ni.2225.

A CD74-dependent MHC class I endolysosomal cross-presentation pathway.

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The Biomedical Research Centre, The Michael Smith Laboratories, The Centre for Blood Research, The Brain Research Centre, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.


Immune responses are initiated and primed by dendritic cells (DCs) that cross-present exogenous antigen. The chaperone CD74 (invariant chain) is thought to promote DC priming exclusively in the context of major histocompatibility complex (MHC) class II. However, we demonstrate here a CD74-dependent MHC class I cross-presentation pathway in DCs that had a major role in the generation of MHC class I-restricted, cytolytic T lymphocyte (CTL) responses to viral protein- and cell-associated antigens. CD74 associated with MHC class I in the endoplasmic reticulum of DCs and mediated the trafficking of MHC class I to endolysosomal compartments for loading with exogenous peptides. We conclude that CD74 has a previously undiscovered physiological function in endolysosomal DC cross-presentation for priming MHC class I-mediated CTL responses.

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