Epitope studies with anti-beta 2-glycoprotein I antibodies from autoantibody and immunized sources.
This paper examines the methodology of anti-beta(2)-glycoprotein I (beta(2)-GPI) epitope determination and provides further epitope studies using human sera containing anti-beta(2)-GPI autoantibodies. Studies in this field may be misleading as the antigen coating density using mutant forms of beta(2)-GPI may be below the threshold required for monogamous divalent binding by low affinity anti-beta(2)-GPI autoantibodies, while being easily detected by high affinity anti-beta(2)-GPI from immunized animals. The antigen density threshold effect is found in anti-beta(2)-GPI autoantibodies from humans and from monoclonal anti-beta(2)-GPI derived from mice with models of autoimmune disease. Anti-beta(2)-GPI from an autoimmune mouse and from 18/21 human sera did not bind above background levels to a domain-I-deleted mutant. In addition, single point mutations in domain I result in dramatic changes in the binding of many human sera containing anti-beta(2)-GPI. These findings support a conclusion that domain I of beta(2)-GPI contains significant epitopes for the anti-beta(2)-GPI antibodies found in the antiphospholipid syndrome.
Reddel
S W
SW
Department of Immunology, Allergy & Infectious Diseases, Division of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Wang
Y X
YX
Sheng
Y H
YH
Krilis
S A
SA
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011817:Rabbits; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D001324:Autoantigens; D000939:Epitopes; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I