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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 and Ram Raj Singh

Autoimmunity and Tolerance Laboratory, Division of Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267

Address correspondence to Dr. Ram Raj Singh, Department of Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 563, Cincinnati, OH 45267-0563. Phone: 513-475-6983; Fax: 513-475-6415; E-mail: singhrm{at}email.uc.edu

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.

Key Words: animal models • peptides • systemic lupus erythematosus • T cell epitopes • T cells

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