Human IgG Monoclonal Anti-αIIbβ3-Binding Fragments Derived from Immunized Donors Using Phage Display

摘要: Previous studies of the immune response in polytransfused Glanzmann thrombasthenia (GT) patients and autoimmune thrombocytopenic purpura (AITP) have relied on serum analysis shown frequent development Abs directed against alpha(IIb)beta(3) integrin. However, little is known about molecular diversity humoral to due paucity mAbs issuing from these pathologies. We isolated human IgG anti-alpha(IIb)beta(3) binding fragments using combinatorial libraries single-chain created B cells a GT an AITP patient, both with Abs. Ab screening was performed activated platelets or alpha(IIb)beta(3)-expressing Chinese hamster ovary cells. Sequencing selected phage showed that broad selection genes virtually all V gene families had been used, indicating response. About one-half V(H) V(L) segments our displayed extensive hypermutations complementarity-determining region, supporting idea Ag-driven occurring patients. The H chain region 3 revealed motifs other than well-known RGD KQAGDV integrin-binding sequences. To knowledge, study first illustrate multiple reactivities structural variations linked anti-platelet Human preferentially form integrin were further characterized because platelet inhibitors are potential therapeutic reagents for treating acute coronary syndromes. Currently available antagonists do not specifically recognize