A competitive mechanism for staphylococcal toxin SSL7 inhibiting the leukocyte IgA receptor, Fc alphaRI, is revealed by SSL7 binding at the C alpha2/C alpha3 interface of IgA.
Leukocyte recruitment and effector functions like phagocytosis and respiratory burst are key elements of immunity to infection. Pathogen survival is dependent upon the ability to overwhelm, evade or inhibit the immune system. Pathogenic group A and group B streptococci are well known to produce virulence factors that block the binding of IgA to the leukocyte IgA receptor, Fc alphaRI, thereby inhibiting IgA-mediated immunity. Recently we found Staphylococcus aureus also interferes with IgA-mediated effector functions as the putative virulence factor SSL7 also binds IgA and blocks binding to Fc alphaRI. Herein we report that SSL7 and Fc alphaRI bind many of the same key residues in the Fc region of human IgA. Residues Leu-257 and Leu-258 in domain C alpha2 and residues 440-443 PLAF in C alpha3 of IgA lie at the C alpha2/C alpha3 interface and make major contributions to the binding of both the leukocyte receptor Fc alphaRI and SSL7. It is remarkable this S. aureus IgA binding factor and unrelated factors from streptococci are functionally convergent, all targeting a number of the same residues in the IgA Fc, which comprise the binding site for the leukocyte IgA receptor, Fc alphaRI.
Wines
Bruce D
BD
Helen Macpherson Smith Trust Inflammatory Disease Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Victoria 3084, Australia. b.wines@ari.unimelb.edu.au
Willoughby
Natasha
N
Fraser
John D
JD
Hogarth
P Mark
PM
D015703:Antigens, CD / Q000737:chemistry; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D005098:Exotoxins / Q000633:toxicity*; D006801:Humans; D007070:Immunoglobulin A / Q000502:physiology; D007141:Immunoglobulin Fc Fragments / Q000097:blood / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence / Q000276:immunology
D015703:Antigens, CD; D005098:Exotoxins; C036832:Fc(alpha) receptor; C045281:IgA receptor; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc; D011994:Recombinant Proteins; C416085:staphylococcal exotoxin 1