Re-establishing tolerance to DNA in humanized and murine models of SLE.
DNA-specific B cells in SLE represent a logical target for therapeutic intervention. We hypothesize that it is possible to re-establish tolerance to native DNA in SCID mice with cells transferred from SLE patients or from lupus-prone MRL/lpr mice by administering chimeric molecules, containing a monoclonal antibody against inhibitory B cell receptors coupled to a peptide that antigenically mimics DNA. These protein-engineered molecules are able to co-crosslink selectively the antigen receptors of B cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.
Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Kalina
K
Nikolova
Nikolina
N
Mihaylova
Elisaveta
E
Voynova
Nikola
N
Kerekov
Vera
V
Gesheva
Jozsef
J
Prechl
Maria
M
Nikolova
Andrey
A
Tchorbanov
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics* / Q000276:immunology; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D032701:Biomimetics; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D025461:Feedback, Physiological; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000639:trends; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D015202:Protein Engineering
D000974:Antibodies, Antinuclear; D018033:Antibodies, Bispecific; D004247:DNA