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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 7/2007

01-07-2007 | Original Article

Comprehensive epitope mapping of the Epstein–Barr virus latent membrane protein-2 in normal, non tumor-bearing individuals

Authors: Maurizio Provenzano, Silvia Selleri, Ping Jin, Ena Wang, Rosemary Werden, Stephanie Slezak, Sharon D. Adams, Monica C. Panelli, Susan F. Leitman, David F. Stroncek, Francesco M. Marincola

Published in: Cancer Immunology, Immunotherapy | Issue 7/2007

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Abstract

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.
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Metadata
Title
Comprehensive epitope mapping of the Epstein–Barr virus latent membrane protein-2 in normal, non tumor-bearing individuals
Authors
Maurizio Provenzano
Silvia Selleri
Ping Jin
Ena Wang
Rosemary Werden
Stephanie Slezak
Sharon D. Adams
Monica C. Panelli
Susan F. Leitman
David F. Stroncek
Francesco M. Marincola
Publication date
01-07-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 7/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0246-3

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