ReviewFc γ receptors
Section snippets
How Fcγ receptors bind IgG
The Fc region is separated from the antigen binding parts of the IgG molecule by a flexible hinge region and forms two structural domains, the CH2 and CH3 domains. Cellular and structural approaches have shown that the lower hinge region contains the major binding site for FcγR. It is established that cross-linking of FcγR membrane molecules is a prerequisite to IgG-mediated cell activation. Since the Fc portion is composed of two identical polypeptide chains which are related to each other by
Roles of Fcγ receptors in autoimmunity
Mice deleted for the ITAM-bearing signal-transducing γ chain associated to FcγRI and FcγRIII or for their respective ligand binding chains have impaired in vitro IgG-dependent phagocytic and ADCC responses (Table 2) [20], [21], [22]. Since the γ chain is associated to the high affinity receptor for IgE, the γ-chain deficient mast cells are unable to respond not only to IgG but also to IgE. These mice are unable to mount type I and type III hypersensitivity reactions and are resistant to the
Roles of Fcγ receptors in antibody-based therapies
There has been a renewed interest since few years in the use of mAbs in the diagnostic and treatment of various tumors [33] (Table 4).The most impressive clinical results have been obtained with Rituximab, a chimeric anti-CD20 mAb in the treatment of B cell lymphoma [34]. A humanized mAb that recognizes the human oncoprotein HER-2/neu over-expressed in some breast cancers and other tumors, induces clinical responses [35]. Other mAbs such as Campath-1H or 17-1A produced encouraging results in
Ectopic expression of FcγR on non-hematopoı̈etic tumor cells
The first studies indicating that non-hematopoı̈etic tumors may express FcRs were performed on a variety of experimental tumors [45] and of human cancers [46], [47]. However, the ectopic expression of FcγRs by non-hematopoı̈etic tumor cells was a controversy because of the presence of FcγR positive inflammatory cells at the tumor site [48] and because FcγR expression was lost during short-term culture of tumor cells in vitro [49]. We reinvestigated the expression of FcγRs on human
Conclusion
The knowledge on FcγR functions and structure has indeed progressed a lot since their original discovery by the 70′ s [52], [53], [54], [55]. FcγR are important molecules not only to mediate and control the effectors functions of IgG antibodies, but they also control the autoimmunity-tolerance balance in the periphery. Furthermore, they are major actors of the efficacy of therapeutic antibodies. The recent description of the crystal structure of the FcγR/Fc complex opens new possibilities to
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