Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 42, Issue 7, Pages 1843-1849Publisher
WILEY
DOI: 10.1002/eji.201142167
Keywords
Antigen cross-presentation; Dendritic cells; Kinases; Phosphatases; RNA interference
Categories
Funding
- Fundacao para a Ciencia e Tecnologia [PIC/IC/82991/2007, PTDC/SAU-MII/100780/2008, PTDC/SAU-IMU/110303/2009]
- Fundacao Luso-Americana para o Desenvolvimento
- Human Frontier Science Program
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-IMU/110303/2009, PTDC/SAU-MII/100780/2008, PIC/IC/82991/2007] Funding Source: FCT
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Effective CD8+ T-cell responses against tumor or microbial antigens that are not directly expressed in antigen-presenting cells (APCs) depend on the cross-presentation of these antigens on MHC class I in APCs. To identify signaling molecules that regulate cross-presentation, we used lentiviral-based RNA interference to test the roles of hundreds of kinases and phosphatases in this process. Our study uncovered eight previously unknown genes, consisting of one positive and seven negative regulators of antigen cross-presentation. Depletion of Acvr1c, a type I receptor for TGF-beta family of signaling molecules, led to an increase in CD80 and CD86 co-stimulator surface expression and secreted IL-12 in mouse bone marrow-derived DCs, as well as antigen-specific T-cell proliferation.
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