The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized.
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.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell