CRYSTAL-STRUCTURE OF AN ANTI-ANTI-IDIOTYPE SHOWS IT TO BE SELF-COMPLEMENTARY

The structure of the Fab fragment of the mouse anti-anti-idiotypic mon oclonal antibody (mAb) GH1002 was solved by X-ray crystallography. mAb GH1002 was elicited with the syngeneic anti-idiotype mAb MK2-23 which mimics the determinant defined by anti-human high molecular weight-me lanoma associated antigen (HMW-MAA) mAb 763.74. The Fab fragments of m Ab GH1002 exist in the crystal as dimers related by crystallographic 2 -fold axes. The interface between dyad-related Fab fragments is formed primarily by interaction of the hypervariable loops of one with the o ther. The self-interaction of Fab fragments of anti-antiidiotypic mAb GH1002 through their combining sites is extremely tight and intricate, closely resembling that observed in structures of id-anti-id complexe s, and comparable in terms of total contact area, charge complementari ty, and number of hydrogen bonds. The self-complementarity of the anti body observed here could be coincidental and thus reflect some non-spe cific binding capability It might, on the other hand, be immunological ly relevant and exemplify a certain degree of evolved self complementa rity characteristic of antibodies participating in idiotypic cascades. (C) 1996 Academic Press Limited