Isotype switch variant anti-idiotype monoclonal antibodies: comparative radiolabeling and in vitro binding.
The influence of antibody isotype on radiolabeling efficacy and immunoreactivity has been difficult to systematically examine as antibodies of different isotypes generally vary in both constant and variable regions. The recent ability to isolate class or isotype switch monoclonal antibodies that have identical binding regions but different constant regions allows for such a comparison to be undertaken. Two isotype switch variant families of murine anti-idiotypic monoclonal antibodies were studied for radioiodination efficacy and immunoreactivity following labeling. In one of the families (S3H5), the IgG2a isotype switch variant derived from an IgG2b parent had nearly 70% greater iodine incorporation and over 50% greater immunoreactivity than the IgG2b parent. In the other family (S5A8), the IgG2a isotype switch variant had virtually identical efficacy of iodine incorporation and binding to antigen after labeling as did its IgG2b parent. Differences in relative heavy and light chain iodine incorporation were seen among isotype switch variants and their parents regardless of alterations in quantitative iodine incorporation or immunoreactivity. We conclude that in certain instances, cloning of an isotype switch variant antibody can result in an antibody offspring that has superior radiolabeling characteristics to its parent antibody. This isotype switching approach may find utility in converting highly-specific, but difficult to label antibodies, to more useful agents.
Wahl
R L
RL
University of Michigan Medical Center, Department of Internal Medicine and Radiology, Ann Arbor 48109-0028.
Wissing
J R
JR
Kaminski
M S
MS
D000818:Animals; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007132:Immunoglobulin Isotypes; D007134:Immunoglobulin Switch Region; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D051379:Mice
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007132:Immunoglobulin Isotypes; D007457:Iodine Radioisotopes