PMID- 12806275
OWN - NLM
STAT- MEDLINE
DCOM- 20040106
LR  - 20191107
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 26
IP  - 3
DP  - 2003 May-Jun
TI  - Identification of a naturally processed HLA-DR-restricted T-helper epitope in 
      Epstein-Barr virus nuclear antigen type 1.
PG  - 212-21
AB  - Epstein-Barr virus nuclear antigen type 1 (EBNA1), the only viral protein that is 
      unequivocally expressed in all Epstein-Barr virus (EBV)-associated malignant 
      diseases, is essential for viral DNA replication and maintenance of the viral 
      episome in infected cells. A glycine-alanine repeat domain inhibits antigen 
      processing through the ubiquitin-proteasome pathway for presentation on human 
      leukocyte antigen (HLA) class I molecules. EBNA1 is not protected from the HLA 
      class II processing pathway, and CD4+ HLA class II-restricted T cells recognize 
      the antigen. CD4+ T-helper (Th) cells play critical roles in initiating, 
      regulating, and maintaining immune responses against viral infections and tumors, 
      so that inclusion of EBNA1 as a target antigen may improve immunotherapy for 
      EBV-associated cancers. In this study, the authors used the TEPITOPE software 
      program to predict promiscuous class II epitope candidates. After several 
      HLA-DR-restricted peptides were identified by in vitro analysis of the T-cell 
      response to synthetic peptides, a T-cell clone was established that was specific 
      for one of the peptides. Functional studies were performed with this clone. The 
      CD4+ T helper cells specific for the HLA-DR15-restricted peptide EBNA1(482) 
      (AEGLRALLARSHVER) recognized naturally processed EBNA1 protein. This epitope was 
      presented by several HLA-DR alleles, including DR4, DR7, and DR11. The inclusion 
      of the promiscuous, naturally processed EBNA1(482) epitope in vaccine constructs 
      could enhance immune responses against EBV-positive cancers.
FAU - Kruger, Stefan
AU  - Kruger S
AD  - Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, 
      Baylor College of Medicine, Houston, Texas, USA.
FAU - Schroers, Roland
AU  - Schroers R
FAU - Rooney, Cliona M
AU  - Rooney CM
FAU - Gahn, Benedikt
AU  - Gahn B
FAU - Chen, Si-Yi
AU  - Chen SY
LA  - eng
GR  - AI48711/AI/NIAID NIH HHS/United States
GR  - CA90427/CA/NCI 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 Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - O5GA75RST7 (EBV-encoded nuclear antigen 1)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Line
MH  - *Epitopes, T-Lymphocyte
MH  - Epstein-Barr Virus Nuclear Antigens/*immunology
MH  - HLA-DR Antigens/genetics/*immunology
MH  - Humans
MH  - Molecular Sequence Data
EDAT- 2003/06/14 05:00
MHDA- 2004/01/07 05:00
CRDT- 2003/06/14 05:00
PHST- 2003/06/14 05:00 [pubmed]
PHST- 2004/01/07 05:00 [medline]
PHST- 2003/06/14 05:00 [entrez]
AID - 10.1097/00002371-200305000-00005 [doi]
PST - ppublish
SO  - J Immunother. 2003 May-Jun;26(3):212-21. doi: 10.1097/00002371-200305000-00005.