Chimeric FcγR have been generated between the mouse high affinity receptor for IgG (FcγRI) and the low affinity receptor for IgG (FcγRII) by exchanging the first two domains of the three-domain extracellular structure of FcγRI with the homologous two-domain extracellular structure of FcγRII. Studies of the affinity and specificity of binding of mouse Ig classes to these receptors defined functional regions of FcγRI and showed some surprising results. After removal of the third extracellular domain of FcγRI, the remaining two domains (domains 1 and 2) retained the capacity to bind Ig in the form of immune complexes, however, they bound monomeric IgG2a with a reduced affinity. Surprisingly, these two domains in the absence of the third domain bound not only IgG2a but also IgG1 and IgG2b, i.e., the third domain of FcγRI suppresses the intrinsic capacity of the first two domains to act as a low affinity FcγRII-like molecule. Linking the third extracellular domain of FcγRI to the two extracellular domains of FcγRII resulted in a receptor that retained the specificity and affinity of FcγRII. Thus, the removal of domain 3 from FcγRI resulted in the conversion of FcγRI to an 'FcγRII-like' receptor. These findings indicate that domains 1 and 2 of FcγRI form an Ig-binding motif, and although domain 3 is not essential for Fc binding by FcγRI, it plays a crucial role in determining the specific high affinity interaction of FcγRI with IgG2a.
|Number of pages||6|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Jan 1991|