Crystal structure of an Fv-Fv idiotope-anti-idiotope complex at 1.9 A resolution.
Anti-idiotopic antibodies react with unique antigenic features, usually associated with the combining sites, of other antibodies. They may thus mimic specific antigens that react with the same antibodies. The structural basis of this mimicry is analyzed here in detail for an anti-idiotopic antibody that mimics the antigen, hen egg-white lysozyme. The crystal structure of an anti-hen-egg-white lysozyme antibody (D1.3) complexed with an anti-idiotopic antibody (E5.2) has been determined at a nominal resolution of 1.9 A. E5.2 contacts substantially the same residues of D1.3 as lysozyme, thus mimicking its binding to D1.3. The mimicry embodies conservation of hydrogen bonding: six of the 14 protein-protein hydrogen bonds bridging D1.3-E5.2 are structurally equivalent to hydrogen bonds bridging D1.3-lysozyme. The mimicry includes a similar number of van der Waals interactions. The mimicry of E5.2 for lysozyme, however, does not extend to the topology of the non-polar surfaces of E5.2 and lysozyme, which are in contact with D1.3 as revealed by a quantitative analysis of the contacting surface similarities between E5.2 and lysozyme. The structure discussed herein shows that an anti-idiotopic antibody can provide an approximate topological and binding-group mimicry of an external antigen, especially in the case of the hydrophilic surfaces, even though there is no sequence homology between the anti-idiotope and the antigen.
Braden
B C
BC
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville 20850, USA.
Fields
B A
BA
Ysern
X
X
Dall'Acqua
W
W
Goldbaum
F A
FA
Poljak
R J
RJ
Mariuzza
R A
RA
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000235:genetics; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000235:genetics; D002645:Chickens; D018360:Crystallography, X-Ray; D005260:Female; D006860:Hydrogen Bonding; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D018716:Molecular Mimicry / Q000276:immunology; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry / Q000276:immunology; D009154:Mutation; D011487:Protein Conformation; D013499:Surface Properties
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D007128:Immunoglobulin Fragments; D007130:Immunoglobulin Idiotypes; C055966:immunoglobulin Fv; D009113:Muramidase