RUBELLA VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES - IDENTIFICATION OF THE CAPSID AS A TARGET OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED LYSIS AND DEFINITION OF 2 EPITOPES

The role of major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T lymphocytes in immunity to rubella virus (RV) infecti on is unknown. Lymphocytes of RV-immune individuals were prestimulated on an RV-infected MHC class I-matched (or partially matched) fibrobla st monolayer which generated CD8+ lymphoblasts capable of lysing RV-in fected fibroblast targets in a class I-restricted manner. Using an inf ectious Sindbis virus (SV) vector which expressed the RV capsid protei n (SV/RubC), lymphocytes from 17 of 22 RV-immune individuals prestimul ated on RV-infected fibroblast monolayers lysed SV/RubC-infected fibro blast targets. A sequence within the amino terminus of the capsid prot ein that was previously shown to contain immunodominant class II-restr icted T-cell epitopes was evaluated for class I-restricted epitopes. F ibroblast targets pulsed with synthetic peptides representing subseque nces within C1 to C29 (subscripts indicate amino acid positions) were lysed effectively when the targets and effectors matched at multiple c lass I alleles. By limiting the number of matching class I alleles, an A2-restricted epitope was identified within C-9 to C22 and an epitope that could be presented by multiple class I molecules was identified within C-11 to C29. A sequence such as C1 to C29 which contains both M HC class I- and MHC class II-restricted epitopes recognized by a heter ologous human population may serve as a component of an effective synt hetic vaccine.