IgG Fc receptor III homologues in nonhuman primate species: genetic characterization and ligand interactions.
Ig Fc receptors bind to immune complexes through interactions with the Fc regions of specific Ab subclasses to initiate or inhibit the defense mechanisms of the leukocytes on which they are expressed. The mechanism of action of IgG-based therapeutic molecules, which are routinely evaluated in nonhuman primate models, involves binding to the low-affinity FcRIII (CD16). The premise that IgG/CD16 interactions in nonhuman primates mimic those present in humans has not been evaluated. Therefore, we have identified and characterized CD16 and associated TCR zeta-chain homologues in rhesus macaques, cynomolgus macaques, baboons, and sooty mangabeys. Similar to humans, CD16 expression was detected on a lymphocyte subpopulation, on monocytes, and on neutrophils of sooty mangabeys. However, CD16 was detected only on a lymphocyte subpopulation and on monocytes in macaques and baboons. A nonhuman primate rCD16 generated in HeLa cells interacted with human IgG1 and IgG2. By contrast, human CD16 binds to IgG1 and IgG3. As shown for humans, the mAb 3G8 was able to block IgG binding to nonhuman primate CD16 and inhibition of nonhuman primate CD16 N-glycosylation enhanced IgG binding. Clearly, differences in interaction with IgG subclasses and in cell-type expression should be considered when using these models for in vivo evaluation of therapeutic Abs.
Rogers
Kenneth A
KA
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Scinicariello
Franco
F
Attanasio
Roberta
R
D000595:Amino Acid Sequence; D000818:Animals; D001666:Binding Sites, Antibody; D016664:Cercocebus; D006367:HeLa Cells; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D048529:Papio hamadryas; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D008024:Ligands; D017452:Receptors, IgG