Differential signal requirements in T-cell activation by mitogen and superantigen.
The requirement for co-stimulatory molecules in T-cell stimulation by mitogens and superantigens in the absence of antigen-presenting cells (APC) was investigated. Phytohemagglutinin (PHA) induced interleukin (IL)-2 receptor (IL-2R) expression on purified T-cells, but proliferation occurred only when exogenous IL-2 was added. In contrast, the proliferative response to a pepsin-extracted type 5 M-protein from Streptococcus pyogenes (pep M5), a recently identified superantigen, required signals provided by phorbol 12-myristate 13-acetate (PMA), IL-1 and IL-6. pep M5 alone did not induce IL-2R expression; however, when combined with PMA, IL-1 and IL-6, IL-2R was expressed. Differences were also observed in the response of the leukemic T-cell line, Jurkat, to PHA and pep M5. Soluble PHA, but not pep M5, induced IL-2 production by these cells in the presence of PMA. Cross-linking by its specific antibody or adsorption of pep M5 to microtiter plates was required to activate Jurkat cells. Both PHA and pep M5 induced Ca2+ mobilization in Jurkat cells; however, only PHA induced a rise in intracellular Ca2+ in purified T-cells, whereas pep M5 was unable to induce this activity unless IL-1, IL-6 and PMA were added. Our data provide biochemical evidence that mitogenic and superantigenic stimulation of T-cells is different.
Majumdar
G
G
Veterans Administration Medical Center, Research Service, Memphis, TN 38104.
Beachey
E H
EH
Tomai
M
M
Kotb
M
M
D000938:Antigen-Presenting Cells / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D008934:Mitogens; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; C014689:streptococcal M protein; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium