Two Ia.17-specific monoclonal antibodies detect the same epitope but do not share idiotype

The clonal diversity of anti-Ia antibodies was studied by using heterologous anti-idiotypic reagents generated against two Ia.17-specific monoclonal antibodies (Mab). The Mab 10-2.16 and 10-3.6 are specific for the Ia.17 public specificity expressed on I-A molecules of the k, s, f, u, r, and j haplotypes. Competitive inhibition experiments demonstrated that 10-2.16 and 10-3.6 inhibited the binding of each other to Ia.17-positive cell targets, indicating that they detected the same or overlapping epitope(s). Identical inhibition patterns of 125I-10-2.16 binding by 10-3.6 by using Ia.17-positive target cells of four different strains indicated that inhibition was not due to steric hindrance from binding to spatially related epitopes. Rabbit anti-10-2.16 serum detected both site-specific and framework-specific 10-2.16 idiotypic determinants not shared by 10-3.6. Conversely, rabbit anti-10-3.6 serum detected 10-3.6 idiotypic determinants not shared by 10-2.16. C3H/J (I-Ak) anti-10-2.16 serum detected only 10-2.16 framework-specific idiotypes, suggesting that 10-2.16 site-specific determinants represent cellular determinants for syngeneic Ia antigens. Furthermore, anti-Ia.17 immune serum from three of 10 mice with the Igh-Cb allotype expressed the 10-2.16 framework-specific idiotype. We have demonstrated that two anti-Ia.17 Mab, 10-2.16 and 10-3.6, lack a shared idiotype, even though they detect a similar epitope. This observation and the variable expression of 10-2.16 idiotypic determinants in immune sera indicate that the B cell response to the Ia.17 epitope detected by 10-2.16 and 10-3.6 is diverse.