Viral proteins expressed by EBV-associated
tumors provide target Ags for
immunotherapy. Adoptive T cell
therapy has proven effective for posttransplant EBV-associated
lymphoma in which all EBV latent Ags are expressed (type III latency). Application of immunotherapeutic strategies to
tumors such as
nasopharyngeal carcinoma and
Hodgkin's lymphoma that have a restricted pattern of EBV Ag expression (type II latency) is under investigation. Potential EBV Ag targets for T cell
therapy expressed by these
tumors include latent
membrane proteins (LMP) 1 and 2. A broad panel of
epitopes must be identified from these target Ags to optimize vaccination strategies and facilitate monitoring of
tumor-specific T cell populations after immunotherapeutic interventions. To date, LMP2
epitopes have been identified for only a limited number of HLA alleles. Using a
peptide library spanning the entire LMP2 sequence, 25 CTL lines from patients with EBV-positive
malignancies expressing type II latency were screened for the presence of LMP2-specific T cell populations. In 21 of 25 lines, T cell responses against one to five LMP2
epitopes were identified. These included responses to previously described
epitopes as well as to newly identified
HLA-A*0206-, A*0204/17-, A29-, A68-, B*1402-, B27-, B*3501-, B53-, and
HLA-DR-restricted
epitopes. Seven of the nine newly identified
epitopes were antigenically conserved among virus isolates from
nasopharyngeal carcinoma tumors. These new LMP2
epitopes broaden the diversity of HLA alleles with available
epitopes, and, in particular, those
epitopes conserved between EBV strains provide valuable tools for
immunotherapy and immune monitoring.