HUMAN CD8(-CELL RESPONSES TO EBV EBNA1 - HLA CLASS-I PRESENTATION OF THE (GLY-ALA)-CONTAINING PROTEIN REQUIRES EXOGENOUS PROCESSING() T)

Epstein-Barr virus (EBV)-induced cytotoxic T lymphocyte (CTL) response s have been detected against many EBV antigens but not the nuclear ant igen EBNA1; this has been attributed to the presence of a glycine-alan ine repeat (GAr) domain in the protein. Here we describe the isolation of human CD8(+) CTL clones recognizing EBNA1-specific peptides in the context of HLA-B35.01 and HLA-A2.03. Using these clones, we show that full-length EBNA1 is not presented when expressed endogenously in tar get cells, whereas the GAr-deleted form is presented efficiently. Howe ver, when supplied as an exogenous antigen, the full-length protein ca n be presented on HLA class I molecules by a TAP-independent pathway; this may explain how EBNA1-specific CTLs are primed in vivo.