The streptococcal superantigen SMEZ exhibits wide allelic variation, mosaic structure, and significant antigenic variation

The frequencies of the newly identified streptococcal superantigen genes sm ez, spe-g, and spe-h were determined in a panel of 103 clinical isolates co llected between 1976 and 1998 at various locations throughout New Zealand. smez and spe-g were found in every group A Streptococcus (GAS) isolate, sug gesting a chromosomal location. The rye-h gene was found in only 24% of the GAS isolates and is probably located on a mobile DNA element. The smez gen e displays extensive allelic Variation and appears to be in linkage equilib rium with the M/emm type. 22 novel smez alleles were identified from 21 dif ferent M/emm types in addition to the already reported alleles smez and sme z-2 with sequence identities between 94.5 and 99.9%. Three alleles are nonf unctional due to a single base pair deletion. The remaining 21 alleles enco de distinct SMEZ variants. The mosaic structure of the smez gene suggests t hat this polymorphism has arisen horn homologous recombination events rathe r than random point mutation. The recently resolved SMEZ-2 crystal structur e shows that the polymorphic residues are mainly sur face exposed and scatt ered over the entire protein. The allelic variation did not affect either V beta specificity or potency, but did result in significant antigenic diffe rences. Neutralizing antibody responses of individual human sera against di fferent SMEZ variants varied significantly. 98% of sera completely neutrali zed SMEZ-1, but only 85% neutralized SMEZ-2, a very potent valiant that has not yet been found in any New Zealand isolate. SMEZ-specific V beta 8 acti vity was found in culture supernatants of 66% of the GAS isolates, indicati ng a potential base for the development of a SMEZ targeting vaccine.