Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns

Abstract

Staphylococcus aureus can produce a wide variety of exotoxins, including toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxins, and staphylococcal enterotoxin-like toxins. These toxins share superantigenic activity. To investigate the ␤ chain (V␤) specificities of each of these toxins, TSST-1 and all known S. aureus enterotoxins and enterotoxin-like toxins were produced as recombinant proteins and tested for their ability to induce the selective in vitro expansion of human T cells bearing particular V␤ T-cell receptors (TCR). Although redundancies were observed between the toxins and the V␤ populations, each toxin induced the expansion of distinct V␤ subsets, including enterotoxin H and enterotoxin-like toxin J. Surprisingly, the V␤ signatures were not associated with a specific phylogenic group of toxins. Interestingly, each human V␤ analyzed in this study was stimulated by at least one staphylococcal superantigen, suggesting that the bacterium derives a selective advantage from targeting the entire human TCR V␤ panel.Staphylococcus aureus produces a broad range of exoproteins, including staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin 1 (TSST-1) (9). These toxins were initially implicated in staphylococcal food poisoning (SEs) and TSS (TSST-1) (39). Since the first characterization of SEA and SEB in 1959 to 1960 by Casman and Bergdoll, 18 different SEs have been described; they are designated SEA to SEV, in the chronological order of their discovery (2,5,41). Some were renamed SE-like toxins (SEl), because either no emetic properties were detected or because they were not tested in primate models (21, 41).SEs, SEls, and TSST-1 share certain structural and biological properties. They have similar sizes (23 to 29 kDa), and their crystal structures, established for SEA, SEB, SEC, SED, SEH, SElI, SElK, and TSST-1, reveal significant homology in their secondary and tertiary conformations (26).

Food-Borne Outbreak Investigation and Molecular Typing: High Diversity of Staphylococcus aureus Strains and Importance of Toxin Detection

“…Depending on the V-beta loops present on T cells, and the V-beta profiles induced upon binding of an SE, different superantigenic activities and thus SAg-related diseases are observed. This variability in human response makes it difficult to determine the SE dose causing symptoms in an individual person [1,3,29]. For outbreak A, the presence of multiple enterotoxins, that might have synergistic effects, cannot be excluded since other enterotoxin genes ( sea , sed , seg , sei , sej and ser ) were detected in the S. aureus isolates.…”

Linezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice

“…SAg are the most powerful biological activators of T lymphocytes and other cells of the immune system (9). Through this property, SAg divert the immune response against the bacterium, thereby helping in bacterial immune evasion (5,15). At the same time, massive immune activation caused by SAg is by itself pathogenic.…”

Persistence survey of Toxic Shock Syndrome toxin-1 producing Staphylococcus aureusand serum antibodies to this superantigen in five groups of menstruating women

“…Other factors not studied in the report include specific V beta 2 TCR (T cell receptor) expansion and human leukocyte antigen (HLA) haplotype [43,44]. …”