A global appraisal of immunodominant CD8 T cell responses to Epstein-Barr virus and cytomegalovirus by bulk screening

Knowledge of the immunodominant responses to Epstein-Barr Virus (EBV) and h uman cytomegalovirus (HCMV) should help to generate cytotoxic T cell lines to these herpesviruses. Here we report on the analysis of CD8 T cell respon ses to EBV and HCMV in the blood of kidney transplant recipients undergoing viral reactivation (n = 16) and in healthy virus carriers (n = 10). We use d a transient COS transfection assay that permits semi-quantitative estimat ion of CD8(+) T cell responses against a larger number of HLA/viral protein combinations within polyclonal T cell lines and thus allows a rapid identi fication of major epitopes. From the comparison of these responses to those that we previously described in the synovial fluid of patients suffering f rom Various forms of chronic arthritis (n = 32), it appears that EBV-specif ic T cells are mainly directed against a restricted set of immunodominant e pitopes, primarily generated during the early lytic cycle and that both IE1 and pp65 are targets of the anti-HCMV response. We suggest that this metho d could be generally applied to the rapid identification of immunodominant T cell epitopes in viral and tumor immunity, and could help selecting HLA-p eptide complexes that could be used to detect and sort specific T cell popu lations.