Amino acid sequence of the region of beta 2-glycoprotein 1 (gp1) which mediates binding of autoantibodies to the cardiolipin-gp1 complex in humans.
Anticardiolipin antibodies (ACA) in sera from patients with autoimmune and infectious diseases were tested for binding to beta 2-glycoprotein 1 (gp1) in order to determine whether human gp1 acts as a cofactor for the binding of ACA to cardiolipin (CL) or as an antigen recognized by ACA. While none of the ACA-positive sera tested recognized gp1 by itself, gp1 was necessary for the binding of ACA to CL in sera from four patients with autoimmune diseases. In three of the four sera the presence of lupus anticoagulant (LA) was detected by prolonged partial thromboplastin time (PTT). Examinations using the bovine equivalent of human gp1 contained in fetal calf serum (FCS) and adult bovine serum (ABS) showed that the human protein can be replaced by the bovine equivalent in the enzyme-linked immunosorbent assay (ELISA). Using affinity-purified antibodies directed against the CL-gp1 complex it was shown that the binding of these antibodies is dependent on the concentration of the bovine gp1 equivalent contained in the formed complex. Similar results found with the human gp1 confirmed this assertion. In order to find out which region of gp1 might mediate the binding between ACA and cardiolipin, we examined to what extent selected oligopeptide sequences of gp1 can substitute for the protein. Peptide P2 (representing the amino acids at positions 268-278 of the gp1 molecule) and gp1 showed about the same binding capacity. Histidine in this peptide seems to be essential for the binding to CL as we found decreased binding with peptides modified in this position. Conclusions from this work show that gp1 does not act as a relevant antigen for ACA, but occupies an essential function in the complex formed with cardiolipin for a certain group of ACA.
Lauer
S A
SA
Institute of Immunology, Medical Academy Dresden, Germany.
Hempel
U
U
Gries
A
A
Frank
K H
KH
D000595:Amino Acid Sequence; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D001053:Apolipoproteins / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000276:immunology*; D006639:Histidine / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D001053:Apolipoproteins; D002308:Cardiolipins; D006023:Glycoproteins; D009842:Oligopeptides; D053482:beta 2-Glycoprotein I; D006639:Histidine