Molecular definition of human β2-glycoprotein (α2-GPI) by cDNA cloning and inter-species differences of β2-GPI in alternation of anticardiolipin binding

Abstract

Human β₂-glycoprotein I (β₂-GPI) is involved in cardiolipin (CL) binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). We examined the inter-species differences of β₂-GPl in alternation of CL binding of aCL. β₂-GPI preparations were obtained from human, bovine, and rat sera by sequential CL-polyacrylamide affinity, DEAE - cellulose, and anti-human IgG-conjugated Sepharose CL-4B column chromatography, and they had apparent molecular weights of 50, 53, and 55 kDa respectively. Human β₂-GPI not only enhanced CL binding by aCL in SLE but also depressed it by those in syphilis. Either bovine and rat β₂-GPI exerted no or quite small inhibition of the binding of syphilitic aCL compared with human β₂-GPI whereas all three species of β₂-GPI generated binding of aCL in SLE to a similar degree. Further, a complete cDNA clone, pβ₂-GPI, was isolated from a human hepatoma cell line, HepG2, and its nucleotide sequence was analyzed. The sequences of bovine and rat counterpart molecules (β₂-GPI) are highly homologous to that of the deduced sequence, and their corresponding regions are 84.0 and 82.5% identical to the complete domain and to the amino acid sequence 53–326 of human β₂-GPI respectively. One of major differences appears at position 154 in human β₂-GPI, and might be associated with the inhibitory effect on the binding of syphilitic aCL. The sequencing analysis of these β₂-GPI proteins might provide leads to functional sites of domains which would be associated with such serological phenomena.