Abstract: The present invention provides domain 1 ?2GPI polypeptides, polynucleotides encoding these polypeptides, mimetics of these polypeptides, and methods using domain 1 ?2GPI polypeptides and mimetics. Domain 1 of ?2GPI has been shown to bind to anti-cardiolipin (?2GPI-dependent antiphospholipid) antibodies, which are associated with several pathologies, such as thrombosis and fetal loss. The domain 1 ?2GPI polypeptides may be used to detect ?2GPI-dependent antiphospholipid antibodies in a sample. The invention further provides methods of inducing tolerance using these domain 1 ?2GPI polypeptides.