Infection with group A streptococci (GAS; Streptococcus pyogenes) causes a wide spectrum of disease ranging from pharyngitis to streptococcal toxic shock syndrome, but the molecular mechanisms that control this range of responses has been unclear. In November 18 Nature Medicine, Malak Kotb and colleagues at the University of Tennessee, Memphis, USA, show that human leukocyte antigen class II allelic variation contributes to differences in the severity of invasive streptococcal infections through their ability to regulate cytokine responses triggered by streptococcal superantigens (Nature Medicine, doi:10.1038/nm800, November 18, 2002).

Kotb et al. determined the distribution of HLA class II haplotypes in patients with invasive GAS infections. They observed that specific human leukocyte antigen class II haplotypes conferred strong protection from severe systemic disease, whereas others increased the risk of severe disease. In addition, they showed that patients with the DRB1*1501/DQB1*0602 haplotype mounted significantly reduced responses and were...

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