| Antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPL) and clinical manifestations. It is unclear why some patients have high levels of aPL, but no clinical symptoms, while others develop APS. Recent studies have demonstrated T cell reactivity to beta2-glycoprotein I (beta2GPI) in patients with APS. To understand why a T cell response develops selectively in some individuals the requirements for antigen presentation and T cell reactivity were evaluated in a murine model of aPL induction. aPL were readily induced in immunized mice, and required MHC class II, but not CD1, antigen presentation. In contrast, induction of a measurable T cell response to beta2GPI necessitated hyperimmunization in the presence of a polyclonal activator. T cells reacted more to reduced, than native, beta2GPI, suggesting that disulfide bond reduction facilitates antigen processing. These results suggest that a T cell response to beta2GPI occurs only in individuals repeatedly exposed to antigen in a proinflammatory environment. |
