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A CD74-DEPENDENT MHC CLASS I ENDOLYSOSOMAL CROSS-PRESENTATION PATHWAY

Immune responses are initiated and primed by dendritic cells (DCs) that cross-present exogenous antigen. The CD74 (invariant chain) chaperone protein is thought to exclusively promote DC priming in the context of MHC class II. However, we demonstrate herein a CD74-dependent MHC class I cross-present...

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Detalles Bibliográficos
Autores principales: Basha, Genc, Omilusik, Kyla, Chavez-Steenbock, Ana, Reinicke, Anna T., Lack, Nathan, Choi, Kyung Bok, Jefferies, Wilfred A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933585/
https://www.ncbi.nlm.nih.gov/pubmed/22306692
http://dx.doi.org/10.1038/ni.2225
Descripción
Sumario:Immune responses are initiated and primed by dendritic cells (DCs) that cross-present exogenous antigen. The CD74 (invariant chain) chaperone protein is thought to exclusively promote DC priming in the context of MHC class II. However, we demonstrate herein a CD74-dependent MHC class I cross-presentation pathway in DCs that plays a major role in the generation of MHC class I restricted, cytolytic T lymphocyte (CTL) responses against viral protein- and cell-associated antigens. CD74 associates with MHC class I molecules in the endoplasmic reticulum of DCs and mediates trafficking of MHC class I to endolysosomal compartments for loading with exogenous peptides. We conclude that CD74 plays a hitherto, undiscovered physiological function in endolysosomal DC cross-presentation for priming MHC class I-mediated CTL responses.