Epitope affinity for MHC class I determines helper requirement for CTL priming

We show here that priming and memory generation of antigen-specific CD8(+) cytotoxic T lymphocytes (CTL) does not require help if the immunogen binds major histocompatibility complex (MHC) class I molecules with high affinity . This conclusion was based on the study of three chemically distinct optim al length CTL epitopes with high affinity for the restriction element K-b. In contrast, when two subdominant epitopes with intermediate MHC binding af finity were studied, either a class II MHC-restricted T helper cell epitope or administration of antibody to CD40 was required to obtain significant C TL priming. Depending on the epitope, one source of help was much more effi cient than the other.