| Abstrakt: |
The high affinity IgG receptor, FcγRI, is comprised of three immunoglobulin superfamily (IgSF) domains (EC1, EC2 and EC3), a single transmembrane spanning region, and a short cytoplasmic tail. We have shown a role for three separate domains of FcγRI in the high affinity binding of IgG. Affinity measurements of chimeric FcγRs in which EC1 and EC2 of FcγRI have been replaced with the homologous EC1 and/or EC2 domains of the low affinity IgG receptor, FcγRII indicate that both EC2 and EC3 are essential for high affinity binding of monomeric IgG. Identification of EC3 from FcγRI as the binding site for the monoclonal antibody 10.1, which blocks IgG binding, provides further evidence for the role of this domain in binding. In addition, we have found that the affinity of FcγRI is increased threefold when co-expressed with its accessory molecule, γ-chain. Affinity measurements of further chimeras indicates that the transmembrane domain of FcγRI has a negative influence upon the affinity of the receptor. To account for these observations, we propose that receptor dimerization is required for maximal affinity of FcγRI. Dimerization may serve as the mechanism by which IgG binding triggers several FcγRI-mediated events.Keywords:CD64/FcγRI/γ-chain/IgG/receptor chimeras |
