viral sequestration of antigen subverts cross presentation to cd8+ t cells病毒的抗原封存颠覆了十字架表示cd8 + t细胞.pdfVIP

Viral Sequestration of Antigen Subverts Cross Presentation to CD8+ T Cells 1 1 1 2 3 3 Eric F. Tewalt , Jean M. Grant , Erica L. Granger , Douglas C. Palmer , Neal D. Heuss , Dale S. Gregerson , 2 1 Nicholas P. Restifo , Christopher C. Norbury * 1 Department of Microbiology and Immunology, Pennsylvania State University, Milton S. Hershey College of Medicine, Hershey, Pennsylvania, United States of America, 2 Surgery Branch and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 3 Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota, United States of America Abstract Virus-specific CD8+ T cells (TCD8+) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross- presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector TCD8+. Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated TCD8+ response to late antigens. We demonstrate that late poxv