Cytotoxic T lymphocyte discrimination between type A Epstein--Barr virus transformants is mapped to an immunodominant epitope in EBNA 3

Abstract

An immunodominant Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte (CTL) epitope, represented by peptide 68, has been mapped to the EBV nuclear antigen, EBNA 3. The epitope is recognized by class I-restricted CTLs through HLA-B8 and is functionally active on type A but not type B lymphoblastoid cell lines (LCLs). Herein we show that peptide 68 is not expressed as a functional CTL epitope by type A LCLs infected with an EBV B95-8 isolate. CTLs from cultures stimulated with autologous type A IARC-BL74 or QIMR-WIL LCLs lysed autologous cells stimulated with phytohaemagglutinin (PHA blasts) and coated with exogenous peptide 68. No peptide 68-specific CTLs were generated in cultures stimulated with autologous type A B95-8 or type B AG876 LCLs. However, the B95-8 LCL coated with peptide 68 was effective in the induction of a peptidespecific CTL response. A peptide 68-specific CTL clone failed to lyse the B95-8 LCL, type B AG876 LCL and PHA blasts, although such targets were lysed when coated with peptide 68.

Antibody reactivity to an Epstein–Barr virus BERF4-encoded epitope occurring also in Asp-57 region of HLA-DQ8 β chain

“…However, in DQS-positive individuals the antibodies were slightly less frequent than in DQS-ncgative individuals, suggesting thai the immune responsiveness may be suppressed in individuals who carry the GPPAA sequence in their HLA-DQ molecules. On the other hand, strain difference of EBV may also explain the clustering of responsiveness in certain families, since the GPPAA sequence is absent from some EBV strains like the prototype-B strain of EBV [18][19][20], As this epitope (GPP.A A) occurs also in the/(chain of HLA-DQ molecules, there is a possibility that EBV infection couid induce imtiiunological cross-reactivity against DQ. This may have relevance particularly in Ihe pathogenesis of type 1 diabetes, since the sequence is the same as in the risk type DQS molecules including alanine at position 57 of DQ /f chain.…”

Cytolytic CD4+-T-Cell Clones Reactive to EBNA1 Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation

“…Their antigen specificity was tested in split-well ELISpot assays. The MS.B11 clone was activated by exposure to HLA-B8-positive LCLs pulsed with 1 M FLRGRAYGL peptide (10,18,34,52,64).…”

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen

“…However, when the.se clones are presented with the natural peptide on target cells transformed with the type A B9,'i-8 strain of EBV, the target epitope is not recognized. This implies the existence of EBV sequence divergence in type A viruses in regions encoding CTL epitopes [12].…”