Episodes of natural selection shaped the interactions of IgA-Fc with FcalphaRI and bacterial decoy proteins.
FcalphaRI, a receptor for IgA-Fc, recruits myeloid cells to attack IgA-coated pathogens. By competing with FcalphaRI for IgA, bacterial decoys, like SSL7 of Staphylococcus aureus, subvert this defense. We examined how pathogen selection has driven the diversification and coevolution of IgA and FcalphaRI. In higher primates, the IgA binding site of FcalphaRI diversified under positive selection, a strong episode occurring in hominoid ancestors about the time of the IgA gene duplication. The differential binding of SSL7 to IgA-Fc of different species correlates with substitution at seven positions in IgA-Fc, two of which were positively selected in higher primates. Two others, which reduce SSL7 binding, emerged during episodes of positive selection in the rabbit and rodent lineages. The FcalphaRI-IgA interaction evolves episodically under two types of positive selection: pressure from pathogen decoys selects for IgA escape variants which, in turn, selects for FcalphaRI variants to keep up with the novel IgA. When FcalphaRI cannot keep up, its function is lost and the gene becomes susceptible to elimination, as occurred in the mouse genome, either by chance or selection on one of the many linked, variable immune system genes. A cluster of positively selected residues presents a putative binding site for unknown IgA-binding factors.
Abi-Rached
Laurent
L
Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dorighi
Kristel
K
Norman
Paul J
PJ
Yawata
Makoto
M
Parham
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001665:Binding Sites; D019143:Evolution, Molecular; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000276:immunology; D002679:Pan troglodytes; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011817:Rabbits; D011961:Receptors, Fc / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D012641:Selection, Genetic; D013211:Staphylococcus aureus / Q000276:immunology*
D015703:Antigens, CD; D001426:Bacterial Proteins; D005098:Exotoxins; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc; C416085:staphylococcal exotoxin 1