Identification of the Immunoglobulin Binding Regions (IBR) of FcγRII and FcɛRI

Fine Structure Analysis of Interaction of FcεRI with IgE

“…As described above, the segment of Fc⑀RI␣-D2 encompassed by residues 87-128 had previously been shown to contain an IgE binding site, which we predicted to be the B-C loop (28). However, when transfected into cells, the ␥109 -116⑀ chimeric receptor containing the Fc⑀RI␣ B-C loop did not bind IgE-EA (Fig.…”

“…To aid in the localization of putative IgE binding regions of Fc⑀RI␣, we have generated a three-dimensional model of the second extracellular domain (D2) of Fc⑀RI␣ based on the known structure of a related domain, CD4-2. CD4-2 belongs to the C2 set of Ig superfamily members, and sequence alignment of Fc⑀RI␣-D2 with CD4-2 suggests that this domain will adopt a similar folding pattern (25,28). The structure of the Fc⑀RI␣-D2 model is characteristic of the C2 Ig-fold, comprising seven ␤-strands (A, B, C, CЈ, E, F, G) that form two antiparallel ␤-sheets of ABE and CCЈFG (Fig.…”

Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG

“…The elucidation of the molecular basis of FcR-Ig interactions is fundamental for understanding the mechanisms by which these receptors mediate biological functions such as activation of inflammatory cells, induction of cytokine release, and destruction of pathogens. In previous studies we utilized chimeric Fc receptors to identify the IgG binding region of human Fc␥RII (18,19 (20). However, despite the direct demonstration of only a single region involved in the binding of IgG, there is compelling evidence to suggest that other regions of Fc␥RII contribute to binding.…”

“…Our previous molecular modeling studies of Fc␥RII domain 2 (wherein the Asn 154 -Ser 161 binding region was located to an exposed loop region; the F/G loop) suggest that these functionally important amino acid changes are situated in the B/C and CЈ/E loops (containing residues 116 and 131, respectively), which are juxtaposed to the F/G loop (contains residue 161) at or near the interface with domain 1 (20). Furthermore, the studies using chimeric Fc␥RII/Fc⑀RI receptors have identified three regions in the structurally homologous receptor, Fc⑀RI, capable of directly binding IgE: residues 87-128, 130 -135, and 154 -161, which encompass the B/C, CЈ/E, and F/G loops respectively (1,18,19). Taken together, these findings suggest that the B/C * This work was supported with the assistance of the National Health and Medical Research Council and Harry Triguboff.…”

Antibody‐dependent Cytotoxicity Mediated by Chimeric Monoclonal Antibody Nd2 and Experimental Immunotherapy for Pancreatic Cancer

“…However, the mechanisms by which chimeric MoAbs exert their in vivo effect in mouse are not clearly understood. Hogarth et al reported that mouse IgG antibodies were usually able to be recognized efficiently by FcγII (which is exhibited on monocytes and neutrophils) and FcγRIII (on NK cells) but not by FcγRI (on monocytes/macrophages), 33) while the Fc portion of chimeric or human IgG antibodies could usually be recognized by not only FcγRII and FcγRIII, but also FcγRI, which has the highest affinity to the Fc portion of immunoglobulin. 34) Furthermore, histological findings of tumors treated with c-Nd2 in the present in vivo study demonstrated necrosis accompanied with strong infiltration of monocytes, and these findings are consisitent with the speculation that the main effector cells inducing ADCC with c-Nd2 are monocytes.…”