Epstein-Barr Nuclear Antigen 1-Specific CD4+ Th1 Cells Kill Burkitt’s Lymphoma Cells

The γ-herpesvirus, EBV, is reliably found in a latent state in endemic Burkitt’s lymphoma. A single EBV gene product, Epstein-Barr nuclear Ag 1 (EBNA1), is expressed at the protein level. Several mechanisms prevent immune recognition of these tumor cells, including a block in EBNA1 presentation to CD8 + killer T cells. Therefore, no EBV-specific immune response has yet been found to target Burkitt’s lymphoma. We now find that EBNA1-specific, Th1 CD4 + cytotoxic T cells recognize Burkitt’s lymphoma lines. CD4 + T cell epitopes of EBNA1 are predominantly found in the C-terminal, episome-binding domain of EBNA1, and ∼0.5% of peripheral blood CD4 + T cells are specific for EBNA1. Therefore, adaptive immunity can be directed against Burkitt’s lymphoma, and perhaps this role for CD4 + Th1 cells extends to other tumors that escape MHC class I presentation.