PMID- 17124584 OWN - NLM STAT- MEDLINE DCOM- 20070622 LR - 20240426 IS - 0340-7004 (Print) IS - 1432-0851 (Electronic) IS - 0340-7004 (Linking) VI - 56 IP - 7 DP - 2007 Jul TI - Comprehensive epitope mapping of the Epstein-Barr virus latent membrane protein-2 in normal, non tumor-bearing individuals. PG - 1047-63 AB - Latent membrane protein (LMP)-2 is one of the Epstein-Barr virus (EBV)-encoded proteins consistently expressed by nasopharyngeal carcinoma (NPC). EBV-transformed lymphoblastoid cell lines (LCL) have been used in patients with NPC to induce LMP-2-recognizing T cell lines which have been in turn utilized for protein-wide mapping of T cell epitopes. However, comprehensive mapping of naturally recognized LMP-2 epitopes in non tumor-bearing individuals has not been reported. Here, we applied a low sensitivity epitope-defining technique for the identification of LMP-2 CTL responses detectable ex vivo in EBV-experienced individuals. This screening tool has been previously validated by analyzing memory CTL responses to Flu, cytomegalovirus (CMV), and the melanoma associated antigen gp100/Mel17. Peripheral blood monocytes (PBMC) from ten Caucasian and ten Chinese individuals were stimulated ex vivo with pools of nonamer (9-mer) peptides overlapping in a stepwise fashion each single amino acid of the LMP-2 sequence. No obvious differences were observed between the immune response of the two ethnic groups save for those related to the divergence in the ethnic prevalence of HLA haplotypes. Several novel and known LMP-2 epitopes were identified. Reactivity toward at least one LMP-2 epitope was detected in 18 of the 20 donors but no prevalent human leukocyte antigen (HLA)/epitope combination was observed confirming that LMP-2 reactivity in the context of common HLA alleles is more pleiotropic than that of FLU and CMV. We believe that the usefulness of these epitopes occurring naturally in non-cancer bearing patients as reagents for the immunization of patients with early or advanced stage NPC deserves further evaluation. FAU - Provenzano, Maurizio AU - Provenzano M AD - Immune Oncology Section, Department of Surgery, University Hospital ZLF, Hebelstrasse 20, 4031 Basel, Switzerland. FAU - Selleri, Silvia AU - Selleri S FAU - Jin, Ping AU - Jin P FAU - Wang, Ena AU - Wang E FAU - Werden, Rosemary AU - Werden R FAU - Slezak, Stephanie AU - Slezak S FAU - Adams, Sharon D AU - Adams SD FAU - Panelli, Monica C AU - Panelli MC FAU - Leitman, Susan F AU - Leitman SF FAU - Stroncek, David F AU - Stroncek DF FAU - Marincola, Francesco M AU - Marincola FM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061124 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (DNA Primers) RN - 0 (EBV-associated membrane antigen, Epstein-Barr virus) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Viral Matrix Proteins) RN - 77238-31-4 (Interferon-beta) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Amino Acid Sequence MH - Asian People MH - Cluster Analysis MH - DNA Primers MH - *Epitope Mapping MH - Epitopes, T-Lymphocyte/*genetics MH - HLA Antigens MH - Herpesvirus 4, Human MH - Humans MH - Interferon-beta/metabolism MH - Interferon-gamma/metabolism MH - Leukocytes, Mononuclear/physiology MH - Molecular Sequence Data MH - Reverse Transcriptase Polymerase Chain Reaction MH - Viral Matrix Proteins/*genetics PMC - PMC11031044 EDAT- 2006/11/25 09:00 MHDA- 2007/06/23 09:00 PMCR- 2006/11/24 CRDT- 2006/11/25 09:00 PHST- 2006/08/14 00:00 [received] PHST- 2006/10/17 00:00 [accepted] PHST- 2006/11/25 09:00 [pubmed] PHST- 2007/06/23 09:00 [medline] PHST- 2006/11/25 09:00 [entrez] PHST- 2006/11/24 00:00 [pmc-release] AID - 246 [pii] AID - 10.1007/s00262-006-0246-3 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2007 Jul;56(7):1047-63. doi: 10.1007/s00262-006-0246-3. Epub 2006 Nov 24.