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

ABSTRACT: 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.

SUBMITTER: Basha G

PROVIDER: S-EPMC4933585 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Basha Genc G Omilusik Kyla K Chavez-Steenbock Ana A Reinicke Anna T AT Lack Nathan N Choi Kyung Bok KB Jefferies Wilfred A WA

Nature immunology 20120205 3

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. ...[more]

PMID: 22306692

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