PMID- 11157061 OWN - NLM STAT- MEDLINE DCOM- 20010607 LR - 20240213 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 193 IP - 3 DP - 2001 Feb 5 TI - Dendritic cells cross-present latency gene products from Epstein-Barr virus-transformed B cells and expand tumor-reactive CD8(+) killer T cells. PG - 405-11 AB - Dendritic cells (DCs) are not targets for infection by the transforming Epstein-Barr virus (EBV). To test if the adjuvant role of DCs could be harnessed against EBV latency genes by cross-presentation, DCs were allowed to process either autologous or human histocompatibility leukocyte antigen (HLA)-mismatched, transformed, B lymphocyte cell lines (LCLs) that had been subject to apoptotic or necrotic cell death. After phagocytosis of small numbers of either type of dead LCL, which lacked direct immune-stimulatory capacity, DCs could expand CD8(+) T cells capable of killing LCLs that were HLA matched to the DCs. Necrotic EBV-transformed, major histocompatibility complex (MHC) class I-negative LCLs, when presented by DCs, also could elicit responses to MHC class II-negative, EBV-transformed targets that were MHC class I matched to the DCs, confirming efficient cross-presentation of LCL antigens via MHC class I on the DC. Part of this EBV-specific CD8(+) T cell response, in both lytic and interferon gamma secretion assays, was specific for the EBV nuclear antigen (EBNA)3A and latent membrane protein (LMP)2 latency antigens that are known to be expressed at low levels in transformed cells. The induced CD8(+) T cells recognized targets at low doses, 1-10 nM, of peptide. Therefore, the capacity of DCs to cross-present antigens from dead cells extends to the expansion of high affinity T cells specific for viral latency antigens involved in cell transformation. FAU - Subklewe, M AU - Subklewe M AD - Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA. FAU - Paludan, C AU - Paludan C FAU - Tsang, M L AU - Tsang ML FAU - Mahnke, K AU - Mahnke K FAU - Steinman, R M AU - Steinman RM FAU - Munz, C AU - Munz C LA - eng GR - R01 AI040874/AI/NIAID NIH HHS/United States GR - AI40874/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (EBV-associated membrane antigen, Epstein-Barr virus) RN - 0 (Epstein-Barr Virus Nuclear Antigens) RN - 0 (Viral Matrix Proteins) SB - IM MH - Antigen Presentation/*immunology MH - Apoptosis/immunology MH - B-Lymphocytes MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Line, Transformed MH - Cross Reactions MH - Dendritic Cells/*immunology MH - Epstein-Barr Virus Nuclear Antigens/*immunology MH - Herpesvirus 4, Human/*immunology MH - Humans MH - Necrosis MH - Phagocytosis/immunology MH - Viral Matrix Proteins/*immunology MH - Virus Latency PMC - PMC2195925 EDAT- 2001/02/07 11:00 MHDA- 2001/06/08 10:01 PMCR- 2001/08/05 CRDT- 2001/02/07 11:00 PHST- 2001/02/07 11:00 [pubmed] PHST- 2001/06/08 10:01 [medline] PHST- 2001/02/07 11:00 [entrez] PHST- 2001/08/05 00:00 [pmc-release] AID - 001325 [pii] AID - 10.1084/jem.193.3.405 [doi] PST - ppublish SO - J Exp Med. 2001 Feb 5;193(3):405-11. doi: 10.1084/jem.193.3.405.