THE STAPHYLOCOCCUS-AUREUS ENTEROTOXIN-B SUPERANTIGEN INDUCES SPECIFICT-CELL RECEPTOR DOWN-REGULATION BY INCREASING ITS INTERNALIZATION

Superantigens are able to stimulate T lymphocyte populations expressin g T cell antigen receptors (TCR) belonging to particular V beta famili es. Moreover, the presence of these superantigens may induce long term unresponsiveness (anergy) of these sensitive cells, Some bacterial to xins are potent superantigens, We have analyzed in vitro the capacity of some Staphylococcus aureus enterotoxin superantigens to modulate T cell antigen receptor expression and the cellular mechanisms involved, Staphylococcus enterotoxin B (SEB) induced rapid down regulation of s urface T cell antigen receptors in V beta 3-expressing T lymphocytes, as assessed by flow cytometry, This phenomenon was a consequence of th e direct interaction between the toxin and the TCR since it was observ ed in the absence of cells expressing major histocompatibility complex class II molecules. The cellular mechanism involved in SEE-induced do wnregulation of TCR was further investigated, Immunofluorescence and c onfocal microscopy experiments showed that toxin B induced intracellul ar accumulation of TCR . CD3 in endocytic vesicles, Moreover, SEE indu ced an increase in T cell receptor endocytosis as measured using radio labeled Fab fragments of an anti-CD3 monoclonal antibody. Taken togeth er, our observations indicate that Staphylococcus enterotoxin B supera ntigen induced changes in the dynamics of surface T cell receptors, wh ich resulted in the fast reduction of membrane receptor numbers,