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J Virol, August 1998, p. 6614-6620, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of a Cytotoxic T-Lymphocyte Response to the Novel BARF0 Protein of Epstein-Barr Virus: a Critical Role for Antigen Expression

Norbert Kienzle,1,* Tom B. Sculley,1 Leith Poulsen,1 Marion Buck,1 Simone Cross,1 Nancy Raab-Traub,2 and Rajiv Khanna1

EBV Unit, Queensland Institute of Medical Research, The Bancroft Centre, Herston, Queensland 4006, Australia,1 and Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 275992

Received 9 February 1998/Accepted 29 April 1998

The Epstein-Barr virus (EBV)-encoded BARF0 open reading frame gene products are consistently expressed in EBV-positive Burkitt's lymphoma (BL) cell lines, nasopharyngeal carcinoma cell lines, and lymphoblastoid cell lines (LCLs). Here we show that the BARF0 sequence includes an HLA A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope. By using theoretically predicted HLA A2 binding motifs and peptide-loaded antigen presentation-deficient T2 cells, polyclonal BARF0-specific CD8+ CTLs were isolated from four different healthy EBV-seropositive donors but not from two seronegative donors. These CTL lines recognized the peptide epitope LLWAARPRL, which was found to be conserved in 33 of 34 virus strains originating from Caucasian, African, and Asian individuals. The BARF0-specific CTL lines could lyse EBV-negative BL cells stably transfected with the BARF0 gene but did not kill HLA A2-matched EBV-positive BL cells and LCLs in a standard 51Cr release assay. Reverse transcriptase PCR analysis demonstrated that these EBV-positive cell lines expressed significantly lower levels of BARF0 mRNA than transfected cells. This data indicated that the BARF0 epitope could be endogenously processed; however, antigen levels in the target cell were a limiting factor for the effective interaction between BARF0-expressing cells and CTLs. The limited expression of BARF0 antigen in EBV-infected BL cells and LCLs might contribute to the escape of immune recognition from virus-specific CTLs present in the host.

* Corresponding author. Mailing address: Queensland Institute of Medical Research, Post Office, Royal Brisbane Hospital, Qld 4029, Australia. Phone: 61-7-33620349. Fax: 61-7-33620106. E-mail: norbertK{at}qimr.edu.au.

J Virol, August 1998, p. 6614-6620, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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