Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I.
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.
Di Pucchio
Tiziana
T
Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, Texas 75204, USA.
Chatterjee
Bithi
B
Smed-Sörensen
Anna
A
Clayton
Sandra
S
Palazzo
Adam
A
Montes
Monica
M
Xue
Yaming
Y
Mellman
Ira
I
Banchereau
Jacques
J
Connolly
John E
JE
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D011992:Endosomes / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D015388:Organelles / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011990:Receptors, Transferrin / Q000378:metabolism
D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D011990:Receptors, Transferrin; D046988:Proteasome Endopeptidase Complex