Article abstract
Nature Immunology 9, 551 - 557 (2008)
Published online: 30 March 2008 | doi:10.1038/ni.1602
Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I
Tiziana Di Pucchio1,2, Bithi Chatterjee3,4, Anna Smed-Sörensen3,4, Sandra Clayton1, Adam Palazzo1, Monica Montes1, Yaming Xue1, Ira Mellman3,4, Jacques Banchereau1 & John E Connolly1
Abstract
Although plasmacytoid dendritic cells (pDCs) respond to virus replication in a nonspecific way by producing large amounts of type I interferon, a rapid, direct function for pDCs in activating antiviral lymphocytes is less apparent. Here we show that pDCs were able to rapidly initiate antigen-specific antiviral CD8+ T cell responses. After being exposed to virus, pDCs efficiently and rapidly internalized exogenous viral antigens and then presented those antigens on major histocompatibility complex (MHC) class I to CD8+ T cells. Processing of exogenous antigen occurred in endocytic organelles and did not require transit of antigen to the cytosol. Intracellular stores of MHC class I partially localized together with the transferrin receptor and internalized transferrin in endosomes, which suggested that such recycling endosomes are sites for loading peptide onto MHC class I or for peptide transit. Our data demonstrate that pDCs use 'ready-made' stores of MHC class I to rapidly present exogenous antigen to CD8+ T cells.
- Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, Texas 75204, USA.
- Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 299 Rome, Italy.
- Ludwig Institute for Cancer Research, Department of Cell Biology and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
- Research Drug Discovery, Genentech, South San Francisco, California 94080, USA.
Correspondence to: John E Connolly1 e-mail: johnconn@baylorhealth.edu
Correspondence to: Jacques Banchereau1 e-mail: jacquesb@baylorhealth.edu