Identification of residues in the first domain of human Fc alpha receptor essential for interaction with IgA

The FcR family contains multiple receptors for Igs, of which the most dista ntly related (similar to 20%) is the IgA receptor (human Fc alpha R), being more homologous (similar to 35%) to another family of killer-inhibitory re ceptor-related immunoreceptors with a 19q13.4 chromosomal location in human s. This study of the Fc alpha R demonstrated that, like several IgG recepto rs, Fc alpha R is a low affinity receptor for Ab (K-a similar to 10(6) M-1) . Rapid dissociation of the rsFc alpha R:IgA complex (t(1/2) similar to 25 s) suggests that monomer IgA would bind transiently to cellular Fc alpha Rs , while IgA immune complexes could bind avidly. Mutagenesis of histidyl 85 and arginyl 82, in the FG loop of domain 1, demonstrated that these residue s were essential for the IgA-binding activity of Fc alpha R, while arginyl 87 makes a minor contribution to the binding activity of the receptor. This site is unusual among the Fc receptors (Fc gamma RII, Fc gamma RIII, and F c epsilon RI), in which the ligand binding site is in domain 2 rather than domain 1, but like Fc alpha R, the FG loop comprises part of the ligand bin ding site. The putative F and G strands flanking the Fc alpha R ligand bind ing site are highly homologous in the other killer-inhibitory receptor-rela ted immunoreceptors, suggesting they comprise a conserved structural elemen t on which divergent EG loops are presented and participate in the specific ligand interactions of each of these receptors.