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. 2003 Jan 2;39(3):177–187. doi: 10.1016/0198-8859(94)90258-5

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

Dawei Ou a, Leslie Ann Mitchell a,b,∗, Margaret Ho a, Diane Décarie a, Aubrey J Tingle a,b, Gerald T Nepom c, Martial Lacroix d, Maan Zrein d
PMCID: PMC7135096  PMID: 7517931

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 (DR4Dw 13A, DR4Dw13B, and DR4KT2) sharing a common residue, glutamic acid at position 74 in their β 1 chains, were able to present SP E1(273–284) to the T-cell clones.

Abbreviations: aa amino acid, Ag antigen, CTL cytotoxic T lymphocyte, EBV-BL Epstein—Barr virus-transformed B-cell line, FFU focus-forming units, HCL HLA homozygous EBV-BL, HLA human leukocyte antigen, mAb murine monoclonal antibody, MHC major histocompatibility complex, PBMNC peripheral blood mononuclear cell, PCR polymerase chain reaction, RAA RV-associated arthritis, rB1BV recombinant RV E1 protein, rIL2 recombinant interleukin 2, RV rubella virus, SP synthetic peptide, TcR T-cell receptor

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