Publication | Open Access
The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized.
86
Citations
0
References
1988
Year
The study tests whether differences in antibody activation arise from cross‑linking orientation or conformational changes, concluding that conformational changes explain potency differences. Using the D10.G4.1 Th cell line that responds to soluble anti‑TCR antibodies, the authors compared anti‑R antibody binding to activation of the line. The authors mapped three distinct epitopes on the R, showing that antibodies targeting the same epitope activate the D10.G4.1 line proportionally to binding, whereas antibodies against different epitopes vary markedly in activation, supporting that conformational changes induced by antibody binding explain potency differences.
Abstract We have used 10 independently isolated mAb reactive with the Ag R on a cloned Th cell line to map three distinct epitopes and three subepitopes on the R. One of these epitopes is clearly on the V beta 8 region, as it is defined by the antibodies KJ-16 and F23.1, known to react with the V beta 8 family of variable regions, and a functional rearranged V beta 8 gene has been cloned from this cell line. Antibodies directed at a second epitope, believed to be on V alpha because it is unaffected by anti-V beta antibodies, are completely inhibited from binding by monoclonal anti-CD3 epsilon-chain antibodies. Because the cloned Th cell line used, D10.G4.1, responds to soluble monoclonal anti-TCR antibodies, it has been possible to compare the binding of anti-R antibodies with their ability to activate this cloned T cell line. We find that for antibodies all specific for the same or a closely related epitope, activation is proportional to binding, by using antibodies that differ by greater than 100-fold in avidity for the R. By contrast, antibodies directed at different epitopes on the R differ markedly in their ability to activate the D10.G4.1 cell line. We have tested whether these differences reflect differences in the orientation of cross-linking the TCR or possible conformational changes induced in the R by the antibodies, and our data support the latter hypothesis as an explanation for the differences in activation potency between antibodies.