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PMID: 15684323 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells.

The Journal of experimental medicine ·Vol. 201 ·No. 3 ·2005-02-07 ·Pages 349-60

Pudney VA, Leese AM, Rickinson AB, Hislop AD

Abstract

Antigen immunodominance is an unexplained feature of CD8+ T cell responses to herpesviruses, which are agents whose lytic replication involves the sequential expression of immediate early (IE), early (E), and late (L) proteins. Here, we analyze the primary CD8 response to Epstein-Barr virus (EBV) infection for reactivity to 2 IE proteins, 11 representative E proteins, and 10 representative L proteins, across a range of HLA backgrounds. Responses were consistently skewed toward epitopes in IE and a subset of E proteins, with only occasional responses to novel epitopes in L proteins. CD8+ T cell clones to representative IE, E, and L epitopes were assayed against EBV-transformed lymphoblastoid cell lines (LCLs) containing lytically infected cells. This showed direct recognition of lytically infected cells by all three sets of effectors but at markedly different levels, in the order IE > E >> L, indicating that the efficiency of epitope presentation falls dramatically with progress of the lytic cycle. Thus, EBV lytic cycle antigens display a hierarchy of immunodominance that directly reflects the efficiency of their presentation in lytically infected cells; the CD8+ T cell response thereby focuses on targets whose recognition leads to maximal biologic effect.

MeSH Terms
Antibody Affinity Antigen Presentation CD8-Positive T-Lymphocytes/immunology Epstein-Barr Virus Infections/immunology Epstein-Barr Virus Nuclear Antigens/immunology HLA Antigens/immunology Humans Immunodominant Epitopes Virus Replication
Chemicals
Epstein-Barr Virus Nuclear Antigens HLA Antigens Immunodominant Epitopes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pudney Victoria A
Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Leese Alison M
Rickinson Alan B
Hislop Andrew D
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20041542
Published
2005-02-07
Epub
2005-00-31
Pages
349-60
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213038
Subset
IM
Grants
Medical Research Council · G9901249 · United Kingdom
External Links
PubMed source DOI: 10.1084/jem.20041542 PMC Full Text View journal details
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