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.
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.
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Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Mitchell
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LA
Ho
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Dćarie
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Tingle
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AJ
Nepom
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GT
Lacroix
M
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Zrein
M
M
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*
D000939:Epitopes; D015804:HLA-DR4 Antigen; D014759:Viral Envelope Proteins; C061826:E1 envelope protein, Rubella virus