Signaling by the Epstein–Barr Virus LMP1 Protein Induces Potent
Signaling by the Epstein–Barr virus LMP1 protein + + induces potent cytotoxic CD4 and CD8 T cell responses Il-Kyu Choia,b, Zhe Wanga,b, Qiang Kea,c, Min Honga,d, Yu Qiana,b, Xiujuan Zhaoa,e, Yuting Liuf, Hye-Jung Kimg, Jerome Ritza,b, Harvey Cantorg, Klaus Rajewskyh,1, Kai W. Wucherpfennigg, and Baochun Zhanga,b,g,1 aDepartment of Medical Oncology, Dana–Farber Cancer Institute, Boston, MA 02215; bDepartment of Medicine, Harvard Medical School, Boston, MA 02115; cDepartment of Diagnostics, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; dDepartment of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China; eDepartment of Cell Biology, Tianjin Medical University, Tianjin 300070, China; fProgram in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115; gDepartment of Cancer Immunology and Virology, Dana–Farber Cancer Institute, Boston, MA 02215; and hImmune Regulation and Cancer, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany Contributed by Klaus Rajewsky, December 9, 2017 (sent for review August 3, 2017; reviewed by Alan B. Rickinson and Susan L. Swain) The B-lymphotropic Epstein–Barr virus (EBV), pandemic in humans, pressive molecules that foster local immune privilege (9, 10). is rapidly controlled on initial infection by T cell surveillance; there- Apparently, host immune cells, particularly T cells, keep EBV- after, the virus establishes a lifelong latent infection in the host. If infected cells under constant surveillance, and EBV-driven ma- surveillance fails, fatal lymphoproliferation and lymphomagenesis + lignancies only arise when surveillance fails. ensue. The initial T cell response consists of predominantly CD8 + T cell responses against EBV-infected or transformed B cells cytotoxic T cells and a smaller expansion of CD4 cells.
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