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 (E1(202) to E1(283), and of a domain of glycoprotein E2 (E2(31) to E2(105). 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.
McCarthy
M
M
Department of Neurology, University of Texas Health Science Center, Houston 77225.
Lovett
A
A
Kerman
R H
RH
Overstreet
A
A
Wolinsky
J S
JS
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002213:Capsid / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D012409:Rubella / Q000276:immunology; D012412:Rubella virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D015678:Viral Structural Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D015678:Viral Structural Proteins; C061827:E2 envelope protein, Rubella virus