Staphylococcal exotoxins deliver activation signals to human T-cell clones via major histocompatibility complex class II molecules.
We investigated whether staphylococcal exotoxins (SEs), in addition to their capacity to induce T-cell activation restricted by the T-cell receptor (TCR) beta-chain variable region, can deliver an activation signal to human T-cell clones through major histocompatibility complex (MHC) class II molecules. Eleven human T-cell clones (9 alpha beta TCR and 2 gamma delta TCR clones) of different antigenic specificities were tested for their capacity to proliferate in response to toxic shock syndrome toxin 1 (TSST-1) and two SEs, SEA and SEB. In the absence of accessory cells, only 4 alpha beta TCR clones were stimulated to proliferate, each by a single SE, and to mobilize intracellular free Ca2+ in response to that SE, events indicative of TCR engagement and, presumably, recognition restricted by the beta-chain variable region. In the presence of accessory cells, each of the 11 T-cell clones was stimulated to proliferate by any one of the three SEs tested. This apparently TCR-unrestricted SE-mediated polyclonal proliferation of T-cell clones occurred in the absence of an increase in intracellular free Ca2+ and was not dependent on the presence of MHC class II expression on accessory cells. In contrast, SE-mediated polyclonal proliferation did not occur in 3 alpha beta TCR clones derived from an MHC class II-deficient patient. Furthermore, all of the three SEs induced the proliferation of 4 natural-killer-cell clones, suggesting that expression of TCR/CD3 complex is not essential for SE-mediated polyclonal proliferation of activated lymphocytes. These results indicate that MHC class II molecules transduce activation signals to human T- and natural-killer-cell clones.
Spertini
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F
Division of Allergy and Immunology, Children's Hospital, Boston, MA.
Spits
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H
Geha
R S
RS
D001427:Bacterial Toxins; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D004261:DNA Replication / Q000187:drug effects; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology*; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D006681:HLA-D Antigens; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D002118:Calcium