T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells.

Abstract

Grampositive bacteria produce a variety of exoproteins, many of which are toxins or otherwise involved in pathogenicity or virulence. The Staphylococcal enterotoxins (SE)' comprise a group of structurally related but serologically distinct proteins produced by certain strains of Straphylococcus aureus (1, 2). Five serological groups (A, B, C, D, and E) of SE have been identified, based on their reactivity with monospecific antisera . SE are the most frequent cause of food poisoning in humans (1, 2) . In addition, SE are the most potent mitogens known, stimulating human or murine lymphocytes at concentrations of <10' M efficiently (3). The only known mitogen active at similarly low concentrations are mAbs against CD3. SE belong to the most widely used mitogens, since SEA and SEB contaminations are the mitogenic principle in Staphylococcal protein A (4). In vivo application of SE leads to polyclonal T cell activation (5) and has significant suppressive effects on cellular and humoral immune responses in vivo (6).The mechanism of T cell activation by SE is unknown. The extremely low concentration of mitogen required for T cell activation suggests a highly selective mechanism in contrast to mitogenic lectins that bind to many structures on T lymphocytes and accessory cells (AC) and require at least 1,000 times higher concentrations .In this report, we have analyzed the molecular mechanism of T cell activation by SE . The experimental data show that reactivity to SE is clonally expressed and that MHC class II molecules are required for T cell triggering by SE. A possible explanation of these findings is that SE are functionally bivalent molecules leading to a selective crosslinking of the T cell receptor/CD3 complex with MHC class II molecules.

Monoclonal antibodies defining functional sites on the toxin superantigen staphylococcal enterotoxin B.

“…binding of toxin to MHC class II molecules is a prerequisite for presentation by LG2 to the T cell hybridomas (6,(21)(22)(23), it is possible that B87 and 2B33 mAbs could have blocked the T cell hybridoma response either by blocking binding of SEB to MHC or by blocking T cell recognition of the toxin/MHC complex. To distinguish these possibilities we tested the ability of the mAbs either to interfere directly with SEB binding to MHC class II or to detect SEB already bound to MHC class II.…”

Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

“…Bacterial toxins, such as those produced by S. aureus, may function as superantigens that may unrestrictedly stimulate B and T cells, resulting in ANCA production (130,(132)(133)(134)(135); however, part of this hypothesis was more or less debunked by the fact that no relationship could be demonstrated between T cell expansion and S. aureus or its superantigens (136). Otherwise, a staphylococcal acid phosphatase may be nephritogenic (137,138) and, bound to endothelial cells, can act as a planted antigen and be recognized by sera of patients with WG (138).…”

Superantigen enhanced protection against a weak tumor-specific melanoma antigen: Implications for prophylactic vaccination against cancer

“…Both CD4 ϩ and CD8 ϩ T cells have been shown to proliferate in response to these superantigens. 2 Furthermore, this massive activation of T cells is accompanied by an increased production of cytokines such as interferon-␥ (IFN-␥). This hyperactivation of T cells generally occurs within 48 hr following superantigen exposure.…”