EBV PEPTIDE EPITOPE SENSITIZATION RESTORES HUMAN CYTOTOXIC T-CELL RECOGNITION OF BURKITTS-LYMPHOMA CELLS - EVIDENCE FOR A CRITICAL ROLE FORICAM-2

The pathogenesis of EBV+ Burkitt's lymphoma (BL) suggests evasion of t he CTL response against EBV Two important features of this tumor have been previously suggested to explain this immune evasion, (a) absence/ low expression of cellular adhesion molecules and (b) restricted expre ssion of EBV latent Ag. To determine the relative importance of these features in relation to evasion of EBV-specific CTL, a group of BL cel l lines with variable expression of the aforementioned phenotypic char acteristics were assayed for specific CTL lysis after exogenous additi on of EBV peptide epitopes. In spite of down-regulated expression of t he adhesion molecules LFA-1, LFA-3, and/or ICAM-1, peptide-sensitized BL cells were recognized and lysed by EBV-specific CTL. Moreover, ther e was no significant difference between the CTL lysis of the BL cells and that of adhesion molecule-positive control cells over a wide range of peptide epitope concentrations. Blocking experiments with mAb to i ndividual adhesion molecules suggested that virus-specific CTL recogni tion of lymphoblastoid cell lines was dependent on an intact LFA-3/CD2 pathway. In contrast, the CTL recognition of peptide-sensitized BL ce lls was critically dependent on the LFA-1/ICAM pathway, with an insign ificant contribution by CD2/LFA-3. The consistently high expression of ICAM-2 on all BL cell lines suggests that the accessory function in C TL recognition of these cells is mediated by the LFA-1/ICAM-2 pathway. Thus, down-regulation of LFA-1, LFA-3, and/or ICAM-1 expression on BL cells does not provide an absolute barrier to tumor cell recognition by virus-specific CTL. The ability of virus-specific CTL to recognize peptide epitope-sensitized BL cells as efficiently as normal cells has demonstrated the importance of latent Ag expression in the CTL contro l of EBV+ tumors.