期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 7, 页码 1843-1849出版社
WILEY
DOI: 10.1002/eji.201142167
关键词
Antigen cross-presentation; Dendritic cells; Kinases; Phosphatases; RNA interference
类别
资金
- 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
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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