Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE.
Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1-B5) that interact with the variable domain of Ig kappa L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1-B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (r(s) = 0.82; p < 0.001) between the maximal percent IL-4 release induced by protein L and that induced by anti-IgE and between intact protein L and the B1-B4 fragment (r(s) = 0.90; p < 0.01). Removal of IgE bound to basophils markedly reduced the IL-4 release induced by anti-IgE, protein L, and B1-B4. Preincubation of basophils with protein L or anti-IgE caused complete cross-desensitization to subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda chains) blocked anti-IgE-induced IL-4 release, but not the releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with kappa L chains of the IgE isotype.
Genovese
Arturo
A
Division of Clinical Immunology and Allergy, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Borgia
Guglielmo
G
Björck
Lars
L
Petraroli
Angelica
A
de Paulis
Amato
A
Piazza
Marcello
M
Marone
Gianni
G
D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D003429:Cross Reactions; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism / Q000502:physiology*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008875:Middle Aged; D009194:Myeloma Proteins / Q000378:metabolism; D010462:Peptostreptococcus / Q000276:immunology / Q000472:pathogenicity; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis*; D020449:Repetitive Sequences, Amino Acid / Q000276:immunology; D018089:Superantigens / Q000502:physiology*
D000888:Antibodies, Anti-Idiotypic; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C055047:Ig L-binding protein, Peptostreptococcus; D007145:Immunoglobulin kappa-Chains; D018793:Interleukin-13; C116593:L-protein, Peptococcus magnus; D009194:Myeloma Proteins; D012333:RNA, Messenger; D017455:Receptors, IgE; D018089:Superantigens; C026408:anti-IgE antibodies; D015847:Interleukin-4; D007073:Immunoglobulin E; D016572:Cyclosporine; C050025:cyclosporin H