title: Analysis of overlapping T- and B-cell antigenic sites on rubella virus E1 envelope protein. Influence of HLA-DR4 polymorphism on T-cell clonal recognition.
abstract: A CTL antigenic site located between residues 273 and 291 of the E1 envelope protein of RV was identified by 51Cr-release assays employing SPs. Two E1-specific CTL clones were examined for immune recognition of RV wild-type and attenuated vaccine strains and recombinant E1 protein. The exact sequence (273-284) recognized by both clones was delineated by using truncated and overlapping SPs covering these residues. The defined T-cell site overlapped almost completely with a virus neutralizing antibody-binding site previously identified with mouse monoclonal and human antibodies. A series of single aa-substituted SP analogues of E1(273-284) was used to define residues critical for T-cell recognition. Using EBV-BL displaying different HLA-DR haplotypes and -DR4 subtypes as targets to determine MHC class II restriction elements, immune recognition by both T-cell clones was shown to be associated with HLA-DR4. Three HLA-DR4 subtypes (DR4Dw13A, DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in their beta 1 chains, were able to present SP E1(273-284) to the T-cell clones.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Ou
authors.forename: L A
authors.initials: LA
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Ho
authors.forename: D
authors.initials: D
authors.lastname: Dćarie
authors.forename: A J
authors.initials: AJ
authors.lastname: Tingle
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
authors.forename: M
authors.initials: M
authors.lastname: Lacroix
authors.forename: M
authors.initials: M
authors.lastname: Zrein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D000939:Epitopes; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012412:Rubella virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D015804:HLA-DR4 Antigen; D014759:Viral Envelope Proteins; C061826:E1 envelope protein, Rubella virus