Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers

Elkington, Rebecca, Walker, Susan, Crough, Tania, Menzies, Moira, Tellam, Judy, Bharadwaj, Mandvi and Khanna, Rajiv (2003) Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. Journal of Virology, 77 9: 5226-5240. doi:10.1128/JVI.77.9.5226-5240.2003


Author Elkington, Rebecca
Walker, Susan
Crough, Tania
Menzies, Moira
Tellam, Judy
Bharadwaj, Mandvi
Khanna, Rajiv
Title Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2003-05-01
Year available 2003
Sub-type Article (original research)
DOI 10.1128/JVI.77.9.5226-5240.2003
Open Access Status DOI
Volume 77
Issue 9
Start page 5226
End page 5240
Total pages 15
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2003
Language eng
Subject C1
320206 Tumor Immunology
730101 Infectious diseases
Abstract Human cytomegalovirus (HCMV) can establish both nonproductive (latent) and productive (lytic) infections. Many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the CD8(+)-T-cell response to HCMV is mainly based on the pp65 antigen. Very little is known about T-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermines the importance of these antigens in several aspects of HCMV disease pathogenesis. In the present study, an efficient and rapid strategy based on predictive bioinformatics and ex vivo functional T-cell assays was adopted to profile CD8(+)-T-cell responses to a large panel of HCMV antigens expressed during different phases of replication. These studies revealed that CD8(+)-T-cell responses to HCMV often contained multiple antigen-specific reactivities, which were not just constrained to the previously identified pp65 or IE-1 antigens. Unexpectedly, a number of viral proteins including structural, early/late antigens and HCMV-encoded immunomodulators (pp28, pp50, gH, gB, US2, US3, US6, and UL18) were also identified as potential targets for HCMV-specific CD8(+)-T-cell immunity. Based on this extensive analysis, numerous novel HCMV peptide epitopes and their HLA-restricting determinants recognized by these T cells have been defined. These observations contrast with previous findings that viral interference with the antigen-processing pathway during lytic infection would render immediate-early and early/late proteins less immunogenic. This work strongly suggests that successful HCMV-specific immune control in healthy virus carriers is dependent on a strong T-cell response towards a broad repertoire of antigens.
Keyword Virology
Epstein-barr-virus
T-cell Responses
Recombinant Vaccinia Infection
Lymphocyte Ctl Response
Class-i
Protein Pp65
Epitopes
Identification
Expression
Specificity
Q-Index Code C1
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 05:32:13 EST