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Downregulation of tap1 in b lymphocytes by cellular and epstein-barr virus-encoded interleukin-10

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http://pubman.mpdl.mpg.de/cone/persons/resource/persons78809

Uebel,  S.
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Zeidler, R., Eissner, G., Meissner, P., Uebel, S., Tampe, R., Lazis, S., et al. (1997). Downregulation of tap1 in b lymphocytes by cellular and epstein-barr virus-encoded interleukin-10. Blood, 90(6), 2390-2397.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-7280-9
Zusammenfassung
Virally infected cells degrade intracellular viral proteins proteolytically and present the resulting peptides in association with major histocompatibility complex (MHC) class I molecules to CD8(+) cytotoxic T lymphocytes (CTLs). These cells are normally prone to CTL-mediated elimination. However, several viruses have evolved strategies to avoid detection by the immune system that interfere with the pathway of antigen presentation. Epstein-Barr virus (EBV) expresses a predominantly late protein, the BCRF1 gene product vIL-10, that is similar in sequence to the human interleukin-10 (hIL-10), We show here that vIL-10 affects the expression of one of the two transporter proteins (TAPs) associated with antigen presentation. Similarly, hIL-10 showed the same activity. Expression of the LMP2 and TAP1 genes but not expression of TAP2 or LMP7 is efficiently downregulated, indicating a specific IL-10 effect on the two divergently transcribed TAP1 and LMP2 genes. Downregulation of TAP1 by IL-10 hampers the transport of peptide antigens into the endoplasmatic reticulum, as shown in the TAP specific peptide transporter assay, their loading onto empty MHC I molecules, and the subsequent translocation to the cell surface. As a consequence, IL-10 causes a general reduction of surface MHC I molecules on B lymphocytes that might also affect the recognition of EBV-infected cells by cytotoxic T cells. (C) 1997 by The American Society of Hematology. [References: 46]