The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction.

Abstract

Toxic shock syndrome toxin 1 (TSST1)t is a 22-kD exotoxin produced by most strains of Staphylococcus aureus isolated from patients with toxic shock syndrome (TSS) (1) . TSST 1 is a potent activator of monocytes and T cells . It acts on monocytes to induce the synthesis of IL-1 and TNF (2-4) . TSSTl also triggers T cell activation and proliferation (5), as well as the production of large amounts of various lymphokines such as IL-2 (6) and IFN-y (7) . The massive induction of monokine and lymphokine production by TSST1 is thought to play an important role in the pathogenesis of TSS.A significant insight into the mechanism of action of TSST 1, as well as other related staphylococcal exotoxins, came with the observation that these toxins bind directly to MHC class II molecules (8-11). Among the MHC class II molecules, TSST1 binds equally well with high affinity and saturation kinetics to HLA-DR and -DQ antigens (8) . TSST 1 also binds to HLA-DP alleles, albeit with a much lower affinity than is observed for HLA-DR and -DQalleles (Scholl, P, unpublished data) . The MHC class II-bound toxin behaves as a superantigen that interacts with T cells via the TCR )3 chain (12, 13) to induce MHC-unrestricted T cell activation and proliferation .The ability ofMHC class II-bound TSST1 to engage T cells raises the possibility that TSST 1 may mimic nominal antigen in initiating cognate interaction between T and B cells resulting in B cell proliferation and Ig production . We demonstrate here that TSST1 induces both the proliferation of resting human B cells and their differentiation into Ig-secreting lymphocytes . Triggering of B cell proliferation and differentiation by TSST1 is dependent on the presence of T cells, and proceeds via This work was supported by U. S .

Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

“…The studies reported here support this hypothesis. While this manuscript was in preparation, Mourad et al reported similar results using the Staphylococcal toxic shock syndrome toxin (13). Together, these two reports suggest that productive Th-B cell bridging may be a common feature of microbial superantigens .…”

Identification of a Novel Gene Cluster Encoding Staphylococcal Exotoxin-Like Proteins: Characterization of the Prototypic Gene and Its Protein Product, SET1

“…Although at least 11 enterotoxins have been identified, it is widely believed that more remain to be discovered, since the known enterotoxin genes do not account for all cases of food poisoning and toxic shock syndrome. Some of the exotoxins are also superantigens, and it has been suggested that they may even play a role in autoimmune diseases (8,18). For instance, the enterotoxins have been suspected of triggering symptoms resembling arthritis in patients with staphylococcal toxic shock syndrome (6,16).…”

A potential role for microbial superantigens in the pathogenesis of systemic autoimmune disease

“…Thus, the superantigen binding may, to some extent, substitute for the cognate T helper-B cell interaction signal and ready B cells that have interacted with antigen to respond more efficiently to lymphokines. In this regard, superantigen binding to class I1 MHC molecules on monocytes results in interleukin-1 and interleukin-6 release (72,90), while Mourad et al report that TSST binding to class I1 MHC molecules on resting human B cells enhances their proliferative response to B cell growth factors (82).…”

“…To approach this question, high-density (resting) tonsillar B cells were isolated on discontinuous Percoll density gradients, incubated with final medium or MAM for 1 hour at 37"C, and washed extensively. B cell populations preincubated with medium alone or with MAM were cultured with MAM-specific T helper cells and assayed for T cell-dependent B cell activation by the cell surface expression of CD23, an early B cell activation antigen (85), and for polyclonal Ig secretion, determined by (82). Thus, at least 2 distinct microbial superantigens bind to class 11 MHC antigens on the surface of resting human B cells and effectively activate autologous superantigen-reactive T helper cells, which in turn trigger polyclonal immunoglobulin production by the superantigen-bearing B cell population.…”