Author/Editor     George, Jacob; Gilburd, Boris; Hojnik, Maja; Levy, Yair; Langevitz, Pnina; Matsuura, Eiji; Koike, Takao; Shoenfeld, Yehuda
Title     Target recognition of Beta 2-glycoprotein I ( beta 2 GPI) - dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of beta 2 GPI in antibody binding
Type     članek
Source     J Immunol
Vol. and No.     Letnik 160
Publication year     1998
Volume     str. 3917-23
Language     eng
Abstract     Beta 2-glycoprotein I (beta 2GPI) is an absolute requirement for the binding of autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target recognition of human beta 2GPI by IgG derived from two patients with primary and two with secondary antiphospholipid syndrome. The total igG serum fractions and beta 2GPI affinity-purified IgGs were assessed by using various domain-deleed mutants (DM) of human beta 2GPI (DMs: I-III, I-IV, III-V, IV-V, and V) and mouse mABs against individual beta 2GPI domains. The four IgGs bound slightly to CL in the absence of beta 2GPI and showed increased binding in the beta 2GPI prsence. Following affinity purification of the IgGs on a beta 2GPI column, reactivity toward CL was absent. DMs containing domain V inhibited the binding of biotinylated beta 2GPI to CL. The addition to CL-coated plates of DM V, but not the other DMs, reduced the binding of all four IgGs. The anti-beta 2GPI IgGs bound only to complete beta 2GPI and DM I-IV on the plates. The binding to plate-adsorbed beta 2GPI could be inhibited by complete beta 2GPI and DM I-IV, the latter being a more efficient inhibitor. Further, the human anti-beta 2GPI IgGs could compete the binding to beta 2 GPI of Cof-21 mouse mAb (directed at domain IV), but not with the two other mouse mAbs. The results suggest that some "autoimmune:" beta 2GPI-dependent anticardiolipin Abs recognize a beta 2 GPI target that is distinct from the CL-binding site in domain V. The target site for some antiphospholipid syndrome IgGs appear to reside in domain IV of beta 2GPI.
Descriptors     ANTIBODIES, ANTICARDIOLIPIN
ANTIPHOSPHOLIPID SYNDROME
GLYCOPROTEINS
MICE
ANTIBODIES, MONOCLONAL
ANTIGEN-ANTIBODY REACTIONS
BINDING SITES
BINDING, COMPETITIVE
IGG
RECOMBINANT PROTEINS
SEQUENCE DELETION