Structure of the Fab Fragment of SDZ CHI621: a Chimeric Antibody Against CD25

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 and k light chain resulting in SDZ CHII621 [Amlot, Rawlings, Fernando, Griffin, Heinrich, Schreier, Castaigne, Moore & Sweny (1995). Transplantation, 60, 748–756]. The Fab fragment of SDZ CHI621 has been purified and crystallized (P2_l, 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 crystallographic R factor 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 V_L and C_L has been strengthened by the chimerization whereas that between V_H and C_H1 has been weakened.