Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG
Lund, J.; Winter, G.; Jones, P.T.; Pound, J.D.; Tanaka, T.; Walker, M.R.; Artymiuk, P.J.; Arata, Y.; Burton, D.R.; Jefferis, R.
Journal of Immunology 147(8): 2657-2662
1991
ISSN/ISBN: 0022-1767 PMID: 1833457 Document Number: 680
Cellular receptors of IgF (Fc.gamma.R) mediate important protective functions. By using site-specific mutants of a chimeric antibody (mouse V H domain and L chain; human IgG3 C H domains), we have demonstrated that human Fc.gamma.RI interacts with a site in the lower hinge of human IgG (residues 234 to 237) and that this interaction dictates Fc.gamma.RI-mediated superoxide generation. Mutations at position 235 resulted in the most profound reductions in Fc.gamma.RI recognition. We have also mapped an interaction site for Fc.gamma.RII to the same region; however, mutations at position 234 and 237 resulted in the greatest reductions in Fc.gamma.RII recognition. The two receptors appear to recognize overlapping but nonidentical sites on the lower hinge of IgG. Deviations from the optimal motif 234-Leu-Leu-Gly-Gly-237 may then explain the human IgG subclass specificity profile for human Fc.gamma.-RI and Fc.gamma.RII.
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