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Vaccination with minigenes encoding V(H)-derived major histocompatibility complex class I-binding epitopes activates cytotoxic T cells that ablate autoantibody-producing B cells and inhibit lupus.

Guo-Chang Fan·Ram Raj Singh
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Abstract

Current treatments for autoantibody-mediated diseases, such as lupus, can cause nonspecific immune suppression. In this paper, we used a bioinformatic approach to identify major histocompatibility complex class I-binding epitopes in the heavy chain variable region of anti-DNA antibodies from lupus-prone (NZB/NZW F1) mice. Vaccination of such mice with plasmid DNA vectors encoding these epitopes induced CD8(+) T cells that killed anti-DNA antibody-producing B cells, reduced serum anti-DNA antibody levels, retarded the development of nephritis, and improved survival. Vaccine-mediated induction of anti-V(H) cytotoxic T lymphocytes that ablate autoreactive B cells represents a novel approach to treat autoantibody-mediated diseases.

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Amino Acid SequenceAnimalsAntibodies, AntinuclearB-LymphocytesComputational BiologyCytokinesDNAEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionLupus Erythematosus, SystemicMiceMice, Inbred BALB CMice, Inbred NZBMolecular Sequence DataT-Lymphocytes, CytotoxicVaccinationJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Guo-Chang Fan, Ram Raj Singh. 2002-09-16. Vaccination with minigenes encoding V(H)-derived major histocompatibility complex class I-binding epitopes activates cytotoxic T cells that ablate autoantibody-producing B cells and inhibit lupus.. https://doi.org/10.1084/jem.20020223

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