Major histocompatibility complex class superantigen binding

Tripp TJ, McCormick JK, Webb JM, Schlievert PM The zinc-dependent major histocompatibility complex class II binding site of streptococcal pyrogenic exotoxin C is critical for maximal superantigen function and toxic activity. Infect Immun 2003 71 1548-1550. 

The First Step Toward Superantigen-Based Intoxication Binding to Major Histocompatibility Complex Class II... 

The staphylococcal superantigens initially bind to conserved elements on major histocompatibility complex class II molecules with relatively high affinity (A(i 10 mol 1 ). These receptors are found in abundance, throughout the body, on antigen-presenting cells such as macrophages and monocytes. However, each toxin... 

Ironically, SE or TSST-1 concentrations that cause T-cell proliferation do not always correlate with receptor affinity. For instance, SEE binds HLA-DR with 100-fold lower affinity relative to the very similarly structured SEA however, SEE stimulates T-cell proliferation to equivalent levels as SEA. The dose-response curves for cytokine and chemokine production in vitro by staphylococcal superantigen-stimulated cells are also very similar despite differences in affmity/specificity for major histocompatibility complex class II and T-cell receptor V/3 molecules. Overall, these observations suggest that the biological effects of staphylococcal superantigens are induced at rather low, nonsaturating occupancy rates not readily classified by typical biokinetics. 

SEA (Leu-48-Gly) and SEB (Phe-44-Ser) mutants unable to bind major histocompatibility complex class II remain emetic but lack T-cell mitogenic effects. " A disulfide loop in SEs, which is absent in the non-enterotoxic TSST-1, may be responsible for the emetic activity of SEs but that too remains controversial. Carboxymethylation of histidines on SEA or SEB generates superantigenic molecules devoid of enter-otoxicity or skin reactivity. This chemically modified SEB also inhibits, perhaps in a competitive fashion, the... 

Staphylococcal enterotoxin B (SEB) is one of seven enterotoxins produced by strains of Staphylococcus aureus. SEB, the best understood of the staphylococcal enterotoxins, can be regarded as the type enterotoxin. Staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and certain other bacterial products (such as streptococcal pyrogenic exotoxins [SPE]) and viral products (which are not discussed in this chapter) are commonly referred to as superantigens because of their profound effects on the immune system. Minute concentrations of superantigens can activate the immune system receptors because they bind with strong avidity to T-cell antigen receptors and class II molecules of the major histocompatibility complex (MHC). 

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