Cytotoxic CD8+ T cells recognize EBV antigen but poorly kill autologous EBV-infected B lymphoblasts: immunodominance is elicited by a peptide epitope that is presented at low levels in vitro

CD8+ T cells play a crucial role in surveillance against EBV-associated malignancies. EBV-specific T cells traditionally have been identified by their ability to kill autologous EBV-transformed B lymphoblastoid cell lines (LCL). Here we report CD8+ cloned and bulk T cells that specifically recognize EBV nuclear Ag EBNA-3C, but do not efficiently kill autologous or HLA-matched LCL. The low cytolysis of these T cells was due to the extremely low density of the antigenic epitope (LDFVRFMGV, EBNA-3C amino acids 285-293) on autologous LCL. The T cells efficiently killed target cells in the presence of < 1 pM synthetic EBNA-3C peptide and, therefore, recognize peptide/HLA complexes with high avidity. Donor T cells with this phenotype were stimulated by autologous LCL and dominated the in vitro EBV-specific response. This indicates that low abundance viral peptides can induce a dominant T cell response.