Multiple binding sites on the CH2 domain of IgG for mouse Fc gamma R11

Lund, J.; Pound, J.D.; Jones, P.T.; Duncan, A.R.; Bentley, T.; Goodall, M.; Levine, B.A.; Jefferis, R.; Winter, G.

Molecular Immunology 29(1): 53-59

1992


ISSN/ISBN: 0161-5890
PMID: 1530984
Document Number: 701
Important mammalian defensive functions such as phagocytosis are triggered in leukocytes by the interaction of the Fc region of IgG with cell surface receptors (Fc.gamma.R). The CH2 domain of IgG has been implicated previously as the site of interaction with human and mouse Fc.gamma.R. This domain was mapped for interaction with mouse Fc.gamma. R11 expressed by the macrophage-like cell line P388D1, using two panels of a total of 32 site-directed mutants of mouse IgG2b and chimeric human IgG3 monoclonal antibodies. Two potential binding sites have been identified: one in or within the vicinity of the lower hinge site on IgG for human Fc.gamma.R1, and one within the binding site on IgG for C1q. The three mutant IgGs (Gly 237 .fwdarw. Ala, Asn 297 .fwdarw. Ala, and Glu 318 .fwdarw. Ala) which do not interact in complexed form also fail to bind as monomers. A 1H NMR study of the three non-binding monomeric mutants suggests that the mutations are largely site-specific, indicating that IgG interacts with mouse Fc.gamma.R11 at two regions within the CH2 domain. This interaction dictates phagocytosis mediated by Fc.gamma.R11 of the P388D1 cell line.

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Multiple binding sites on the CH2 domain of IgG for mouse Fc gamma R11