The IgD CH1 region contains the binding site for the human respiratory pathogen Moraxella catarrhalis IgD-binding protein MID.

The Moraxella catarrhalis IgD-binding protein (MID) has a unique specificity for human IgD, and the sequence with maximal IgD binding is located within the amino acids MID962-1200. In the present paper, we examined the MID binding site on IgD using a series of recombinant Ig. Full-length IgD, IgD F(ab')2, and an IgD F(ab') C290R mutant lacking the inter-heavy-chain cysteine 290 were manufactured. Furthermore, a series of IgD/IgG chimeras were constructed. ELISA, dot blot and flow cytometry were used to study the binding of purified Ig to native MID, recombinant MID962-1200 or to Moraxella with or without MID. MID962-1200 bound both the IgD F(ab')2 and F(ab') C290R, indicating that the binding occurred independently of antibody structure. When amino acids 157-224 of the IgD CH1 region were substituted with IgG sequences, binding by M. catarrhalis or recombinant MID962-1200 was abolished. Subsequent smaller substitutions of IgD CH1 157-224 with IgG sequences led us to conclude that IgD CH1 amino acids 198-206 were crucial for the interaction between MID and IgD.