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 two epitopes.
The role of major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T lymphocytes in immunity to rubella virus (RV) infection is unknown. Lymphocytes of RV-immune individuals were prestimulated on an RV-infected MHC class I-matched (or partially matched) fibroblast monolayer which generated CD8+ lymphoblasts capable of lysing RV-infected fibroblast targets in a class I-restricted manner. Using an infectious Sindbis virus (SV) vector which expressed the RV capsid protein (SV/RubC), lymphocytes from 17 of 22 RV-immune individuals prestimulated on RV-infected fibroblast monolayers lysed SV/RubC-infected fibroblast targets. A sequence within the amino terminus of the capsid protein that was previously shown to contain immunodominant class II-restricted T-cell epitopes was evaluated for class I-restricted epitopes. Fibroblast targets pulsed with synthetic peptides representing subsequences within C1 to C29 (subscripts indicate amino acid positions) were lysed effectively when the targets and effectors matched at multiple class I alleles. By limiting the number of matching class I alleles, an A2-restricted epitope was identified within C9 to C22 and an epitope that could be presented by multiple class I molecules was identified within C11 to C29. A sequence such as C1 to C29 which contains both MHC class I- and MHC class II-restricted epitopes recognized by a heterologous human population may serve as a component of an effective synthetic vaccine.
Lovett
A E
AE
Department of Neurology, University of Texas Health Science Center, Houston 77030.
Hahn
C S
CS
Rice
C M
CM
Frey
T K
TK
Wolinsky
J S
JS
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D000917:Antibody Formation; D016827:CD8 Antigens / Q000276:immunology; D002213:Capsid / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005805:Genes, MHC Class I; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D012409:Rubella / Q000276:immunology*; D012412:Rubella virus / Q000276:immunology*; D012845:Sindbis Virus / Q000235:genetics; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides