Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen.

摘要: Streptococcus pyogenes (group A streptococcus) produces a variety of exotoxins, including the streptococcal pyrogenic exotoxins (SPEs; scarlet fever toxins) that have been implicated in severe invasive diseases such as toxic shock syndrome (STSS) and (reviewed references 29, 37, 51, 54). The SPEs belong to larger group toxin superantigens (PTSAgs) (5) stimulate T cells by binding both invariant regions on major histocompatibility complex (MHC) class II molecules specific Vβ chains T-cell receptor; this activity has termed superantigenicity (36). ability PTSAgs bind receptor (TCR) is independent peptide contained groove MHC molecules, since there are relatively few TCR regions, frequency responding PTSAg exposure exceeds conventional antigens several orders magnitude reference 35). Extensive proliferation results massive cytokine release, which believed contribute most effects STSS. Structural immunological characterization revealed they low-molecular-weight proteins (24,000 28,000) heat protease resistant. Although only C generally considered be associated with STSS (7–9, 16, 17, 41, 45, 55, 58), distinct SPE serotypes now known include (23, 63), B (14), (12), F (46, 64), G (48), H well superantigen (SSA) (40) multiple mitogenic exotoxin Z (SMEZ) (25, 48, 49). However, unlike other serotypes, enzymatic (protease DNase, respectively) (13, 18, 27), neither sequence homology SPEs, not share structural similarity (24). It shown clinical strains S. from patients produce nor (6, 10, 25, 42, 44, 62). This observation raises possibility uncharacterized PTSAgs, related or C, capable causing STSS. Consistent hypothesis, it demonstrated novel fact made virulent streptococci (1, 40). Furthermore, selective depletion certain subsets did correlate patterns (62). Importantly, study also determined many possess genes for A, SSA. Two (SPE H) were recently identified characterized Proft et al. aided genomic database at University Oklahoma. These authors SMEZ-2, very similar previously described SMEZ (25). crystal structures SMEZ-2 reported, conformed generic bacterial folding pattern (1). SMEZ, (at least our current knowledge), highly polymorphic 22 different smez alleles identified. research although polymorphisms (now 1 through 22) maintained their subset stimulatory profiles (Vβ4 Vβ8), resulted antigenic variants (48). During G, H, partial gene putative was named speJ, further (48). present describes cloning, expression, PTSAg, J, we show properties those already-characterized rabbit human cells, Vβ-specific superantigenic activity, lethal two models J represents seventh superantigen, interesting questions about evolution superantigens.