Superantigen enhancement of specific immunity: antibody production and signaling pathways.
Superantigens are microbial proteins that induce massive activation, proliferation, and cytokine production by CD4+ T cells via specific Vbeta elements on the TCR. In this study we examine superantigen enhancement of Ag-specific CD4+ T cell activity for humoral B cell responses to T-dependent Ags BSA and HIV gp120 envelope, type I T-independent Ag LPS, and type II T-independent Ag pneumococcal polysaccharides. Injection of BSA followed by a combination of superantigens staphylococcal enterotoxin A and staphylococcal enterotoxin B (SEB) 7 days later enhanced the anti-BSA Ab response in mice approximately 4-fold as compared with mice given BSA alone. The anti-gp120 response was enhanced approximately 3-fold by superantigens. The type II T-independent Ag pneumococcal polysaccharide response was enhanced approximately 2.3-fold by superantigens, whereas no effect was observed on the response to the type I T-independent Ag LPS. The superantigen effect was completely blocked by the CD4+ T cell inhibitory cytokine IL-10. SEB-stimulated human CD4+ T cells were examined to determine the role of the mitogen-activated protein (MAP) kinase signal transduction pathway in superantigen activation of T cells. Inhibitors of the mitogen pathway of MAP kinase blocked SEB-induced proliferation and IFN-gamma production, while an inhibitor of the p38 stress pathway had no effect. Consistent with this, SEB activated extracellular signal-regulated kinase/MAP kinase as well as MAP kinase-interacting kinase, a kinase that phosphorylates eIF4E, which is an important component of the eukaryotic protein synthesis initiation complex. Both kinases were inhibited by IL-10. Thus, superantigens enhance humoral immunity via Ag-specific CD4+ T cells involving the stress-independent pathway of MAP kinase.
Torres
Barbara A
BA
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Perrin
George Q
GQ
Mujtaba
Mustafa G
MG
Subramaniam
Prem S
PS
Anderson
Amy K
AK
Johnson
Howard M
HM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D018089:Superantigens / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D018089:Superantigens; D012710:Serum Albumin, Bovine; C031818:enterotoxin B, staphylococcal