The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells

Severe bacterial or viral infections can induce a state of immune hyperactivation that can culminate in a potentially lethal cytokine storm. The classic example is toxic shock syndrome, a life-threatening complication of Staphylococcus aureus or Streptococcus pyogenes infection, which is driven by potent toxins known as superantigens (SAgs). SAgs are thought to promote immune evasion via the promiscuous activation of T cells, which subsequently become hyporesponsive, and act by cross-linking major histocompatibility complex class II molecules on antigen-presenting cells to particular beta-chain variable (TRBV) regions of alpha beta T cell receptors (TCRs). Although some of these interactions have been defined previously, our knowledge of SAg-responsive TRBV regions is incomplete. In this study, we found that CD4(+) and CD8(+) T cells expressing TRBV12-3/12-4(+) TCRs were highly responsive to streptococcal pyrogenic exotoxin C (SpeC) and toxic shock syndrome toxin-1 (TSST-1). In particular, SpeC and TSST-1 specifically induced effector cytokine production and the upregulation of multiple coinhibitory receptors among TRBV12-3/12-4(+) CD4(+) and CD8(+) memory T cells, and importantly, these biological responses were dependent on human leukocyte antigen (HLA)-DR. Collectively, these data provided evidence of functionally determinative and therapeutically relevant interactions between SpeC and TSST-1 and CD4(+) and CD8(+) memory T cells expressing TRBV12-3/12-4(+) TCRs, mediated via HLA-DR. In peripheral blood mononuclear cells from healthy human donors, the superantigens SpeC and TSST-1 are shown to specifically activate TRBV12-3/12-4(+) memory T cells.

Automated summary

Severe bacterial or viral infections can lead to an overactive immune response known as a cytokine storm. Superantigens are potent toxins that activate T cells non-specifically, leading to T cell dysfunction and immune evasion. This study found that TRBV12-3/12-4(+) T cells are highly responsive to streptococcal pyrogenic exotoxin C (SpeC) and toxic shock syndrome toxin-1 (TSST-1).