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 monoclonal 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-melanoma associated antigen (HMW-MAA) mAb 763.74. The Fab fragments of mAb 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 other. The self-interaction of Fab fragments of anti-anti-idiotypic mAb GH1002 through their combining sites is extremely tight and intricate, closely resembling that observed in structures of id-anti-id complexes, and comparable in terms of total contact area, charge complementarity, and number of hydrogen bonds. The self-complementarity of the antibody observed here could be coincidental and thus reflect some non-specific binding capability. It might, on the other hand, be immunologically relevant and exemplify a certain degree of evolved self complementarity characteristic of antibodies participating in idiotypic cascades.
Ban
N
N
Department of Biochemistry, University of California at Riverside 92521, USA.
Day
J
J
Wang
X
X
Ferrone
S
S
McPherson
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments