Anti-metatype antibody stabilization of Fv 4-4-20 variable domain dynamics.
Anti-metatype (anti-Met) antibodies are immunoglobulins that specifically recognize and stabilize antibodies in their liganded or metatypic state, but lack specificity for either the hapten or the unliganded antibody. Autologous anti-Met antibodies were previously observed in vivo, suggesting that a metatypic autoantibody response could play a physiological role in the immune network, e.g. controlling the clearance of immune complexes from circulation. The first elicited anti-Met antibodies were against the fluorescein-liganded high affinity murine anti-fluorescein monoclonal antibody 4-4-20. The fluorescein-hapten system has proved to be an invaluable tool for both the recognition and characterization of the metatypic response by utilization of its spectral properties. In this investigation, hydrostatic pressure measurements, in conjunction with fluorescence spectroscopy, were performed on the recombinant Fv derivative (Fv 4-4-20) of the high affinity anti-fluorescein monoclonal antibody 4-4-20 complexed to anti-Met antibodies to study the influence of anti-Met antibodies of Fv 4-4-20 intervariable domain interactions. Anti-Met antibodies bound to liganded Fv 4-4-20 were observed to cause a change in the fluorescence properties of fluorescein that was not observed when anti-Met antibodies were bound to the liganded parent immunoglobulin. The variation of these spectral properties upon addition of anti-Met antibodies was shown to be correlated with dissociation of the variable domains in Fv 4-4-20 in response to its interaction with the anti-Met antibody. The ability to cause variable domain dissociation was dependent on whether monoclonal or polyclonal anti-Met antibodies were bound to the metatype. A model was proposed that elucidated the interaction of anti-Met antibodies, polyclonal and monoclonal, with variable domains of the primary anti-antigen antibody.
Carrero
J
J
Department of Microbiology, University of Illinois at Urbana-Champaign 61801-3797, USA.
Mallender
W D
WD
Voss
E W
EW
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D001666:Binding Sites, Antibody; D006224:Cricetinae; D005452:Fluoresceins; D007700:Kinetics; D008024:Ligands; D051379:Mice; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013050:Spectrometry, Fluorescence
D000906:Antibodies; D000911:Antibodies, Monoclonal; D005452:Fluoresceins; D008024:Ligands; D011994:Recombinant Proteins