Immunodominant T-cell epitopes of rubella virus structural proteins defined by synthetic peptides

Sets of overlapping synthetic peptides containing predicted T-cell epitope motifs were designed from the murine monoclonal antibody-defined map of linear B-cell epitope domains within each of the structural proteins of rubella virus (RV). The peptides represented well-defined subsequences of two capsid domains (C₁ to C₂₉ and C₆₄ to C₉₇), of a domain of glycoprotein E1 containing neutralizing determinants (E1₂₀₂ to E1₂₈₃), and of a domain of glycoprotein E2 (E2₃₁ to E2₁₀₅). With the exception of peptides representing C₆₄ to C₉₇, each set of peptides stimulated varied but individually specific lymphoproliferative responses in peripheral blood mononuclear cells from 25 to 50% of a representatively large number of normal, RV-immune human donors with diverse human leukocyte antigen (HLA) backgrounds. Responses were mediated by CD4⁺ T cells in association with HLA class II antigens, though lymphoproliferative responses to a given peptide were usually not HLA-DR allele specific. Correlation analysis of responses to overlapping peptides suggests that there is an immunodominant T-proliferative epitope within C₁₄ to C₂₉ recognized by approximately 50% of the donor population. However, limiting-dilution analysis indicated much variability between individuals in lymphocyte recognition of this T-cell determinant, even within similar HLA-DR contexts. Thus, the fine specificity of relatively immunodominant T-cell epitopes may vary from individual to individual. Synthetic peptides with predicted T-cell motifs have proved to be useful probes of the molecular determinants of cellular immunity to RV and should expand the rational basis for the design of synthetic RV vaccines.