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.
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.
Fan
Guo-Chang
GC
Autoimmunity and Tolerance Laboratory, Division of Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0563, USA.
Singh
Ram Raj
RR
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D019295:Computational Biology; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D000974:Antibodies, Antinuclear; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D004247:DNA