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The Center for Cell and Gene Therapy [K. S. V., T. F., H. E. H., M. K. B, C. M. R., R-F. W.], and Departments of Immunology [K. S. V., T. F., R-F. W.], Pediatrics and Medicine [H. E. H., M. K.B.], and Pediatrics and Virology and Microbiology [C. M. R.], Baylor College of Medicine, Houston, Texas 77030
The EBV-encoded nuclear antigen 1 (EBNA1) is required for the maintenance and replication of the viral episome in EBV-transformed human B-lymphoblastoid cell lines. It is expressed in all EBV-associated tumors, making it a potentially important target for immunotherapy. However, this promise has not been realized, because an endogenously processed MHC class I-restricted T-cell epitope remains to be identified, and relatively little is known about MHC class II-restricted helper epitopes in the molecule. In this report, we identify a T-cell peptide derived from EBNA1 that is recognized by CD4+ T cells. More importantly, EBNA1-specific, HLA-DP3-restricted CD4+ T cells are capable of recognizing MHC class II-matched Burkitt’s lymphoma cells, autologous peripheral blood mononuclear cells loaded with the purified EBNA1 protein, as well as target cells transfected with Ii-EBNA1 cDNA. These new findings demonstrate that EBNA1 is processed endogenously and presented to T cells by MHC class II molecules, and, hence, may be useful to incorporate into cancer vaccines to enhance antitumor immunity against EBV-associated tumors.
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