PMID- 25355876
OWN - NLM
STAT- MEDLINE
DCOM- 20150316
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 1
DP  - 2015 Jan
TI  - T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr 
      virus.
PG  - 703-12
LID - 10.1128/JVI.02642-14 [doi]
AB  - Polymorphism in the human leukocyte antigen (HLA) loci ensures that the CD8(+) T 
      cell response to viruses is directed against a diverse range of antigenic 
      epitopes, thereby minimizing the impact of virus escape mutation across the 
      population. The BZLF1 antigen of Epstein-Barr virus is an immunodominant target 
      for CD8(+) T cells, but the response has been characterized only in the context 
      of a limited number of HLA molecules due to incomplete epitope mapping. We have 
      now greatly expanded the number of defined CD8(+) T cell epitopes from BZLF1, 
      allowing the response to be evaluated in a much larger proportion of the 
      population. Some regions of the antigen fail to be recognized by CD8(+) T cells, 
      while others include clusters of overlapping epitopes presented by different HLA 
      molecules. These highly immunogenic regions of BZLF1 include polymorphic 
      sequences, such that up to four overlapping epitopes are impacted by a single 
      amino acid variation common in different regions of the world. This focusing of 
      the immune response to limited regions of the viral protein could be due to 
      sequence similarity to human proteins creating "immune blind spots" through 
      self-tolerance. This study significantly enhances the understanding of the immune 
      response to BZLF1, and the precisely mapped T cell epitopes may be directly 
      exploited in vaccine development and adoptive immunotherapy. IMPORTANCE: 
      Epstein-Barr virus (EBV) is an important human pathogen, associated with several 
      malignancies, including nasopharyngeal carcinoma and Hodgkin lymphoma. T 
      lymphocytes are critical for virus control, and clinical trials aimed at 
      manipulating this arm of the immune system have demonstrated efficacy in treating 
      these EBV-associated diseases. These trials have utilized information on the 
      precise location of viral epitopes for T cell recognition, for either measuring 
      or enhancing responses. In this study, we have characterized the T cell response 
      to the highly immunogenic BZLF1 antigen of EBV by greatly expanding the number of 
      defined T cell epitopes. An unusual clustering of epitopes was identified, 
      highlighting a small region of BZLF1 that is targeted by the immune response of a 
      high proportion of the world's population. This focusing of the immune response 
      could be utilized in developing vaccines/therapies with wide coverage, or it 
      could potentially be exploited by the virus to escape the immune response.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Rist, Melissa J
AU  - Rist MJ
AD  - Cellular Immunology Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, Australia School of Medicine, The University of Queensland, Brisbane, 
      Australia.
FAU - Neller, Michelle A
AU  - Neller MA
AD  - Cellular Immunology Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, Australia.
FAU - Burrows, Jacqueline M
AU  - Burrows JM
AD  - Cellular Immunology Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, Australia.
FAU - Burrows, Scott R
AU  - Burrows SR
AD  - Cellular Immunology Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, Australia School of Medicine, The University of Queensland, Brisbane, 
      Australia scott.burrows@qimrberghofer.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141029
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - Trans-Activators/*immunology
PMC - PMC4301143
EDAT- 2014/10/31 06:00
MHDA- 2015/03/17 06:00
PMCR- 2015/06/16
CRDT- 2014/10/31 06:00
PHST- 2014/10/31 06:00 [entrez]
PHST- 2014/10/31 06:00 [pubmed]
PHST- 2015/03/17 06:00 [medline]
PHST- 2015/06/16 00:00 [pmc-release]
AID - JVI.02642-14 [pii]
AID - 02642-14 [pii]
AID - 10.1128/JVI.02642-14 [doi]
PST - ppublish
SO  - J Virol. 2015 Jan;89(1):703-12. doi: 10.1128/JVI.02642-14. Epub 2014 Oct 29.