T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr virus

Rist, Melissa J, Neller, Michelle A, Burrows, Jacqueline M and Burrows, Scott R (2015) T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr virus. Journal of Virology, 89 1: 703-712. doi:10.1128/JVI.02642-14

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Author Rist, Melissa J
Neller, Michelle A
Burrows, Jacqueline M
Burrows, Scott R
Title T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr virus
Journal name Journal of Virology   Check publisher's open access policy
ISSN 1098-5514
Publication date 2015-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1128/JVI.02642-14
Open Access Status File (Publisher version)
Volume 89
Issue 1
Start page 703
End page 712
Total pages 10
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
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.
Keyword Peptide motifs
Class-I
Responses
Molecules
Infection
Binding
Protein
EBV
Transactivators
Immunodominance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Official Audit
School of Medicine Publications
 
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