A specific drug targeted to the IL‐2 receptor on activated T lymphocytes could limit acute immunological rejection during organ transplantation. A high‐affinity monoclonal antibody directed against the α‐chain of the IL‐2 receptor (CD25) was chimerized with the constant regions of the human IgG1 heavy andklight chain resulting in SDZ CHII621 Amlot, Rawlings, Fernando, Griffin, Heinrich, Schreier, Castaigne, MooreSweny (1995).Transplantation,60, 748–756. The Fab fragment of SDZ CHI621 has been purified and crystallized (P2l,a= 39.58,b= 59.76,c= 102.09 Å, β = 99.98°). Its structure has been determined by molecular replacement and refined at 2.6 Å to a crystallographicRfactor of 19.7. The protein exhibits the typical immunoglobulin fold. The complementary determining regions (CDR's) 1 and 2 of both heavy and light chains show similar conformations to other known reported structures whereas the CDR3 from the light chain seems to adopt a novel type of conformation. There is a network of interactions which maintain the CDR3 of both chains together and limit their solvent accessibility. The interaction between VLand CLhas been strengthened by the chimerization whereas that between VHand CH1
展开▼
