The Journal of Experimental Medicine
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Published online 15 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1765/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 10, May 15, 2000 1765-1776

Original Article

The Streptococcal Superantigen SMEZ Exhibits Wide Allelic Variation, Mosaic Structure, and Significant Antigenic Variation

Thomas Profta, S. Louise Moffatta, Kylie D. Wellera, A. Patersona, Diana Martinb, and John D. Frasera
a Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand
b Institute of Environmental Science and Research Limited, Porirua, New Zealand

Correspondence to: John D. Fraser, Department of Molecular Medicine, School of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand. Tel:64-9-373-7599 ext. 6036 Fax:64-9-373-7492 E-mail:jd.fraser{at}auckland.ac.nz.

The frequencies of the newly identified streptococcal superantigen genes smez, spe-g, and spe-h were determined in a panel of 103 clinical isolates collected between 1976 and 1998 at various locations throughout New Zealand. smez and spe-g were found in every group A Streptococcus (GAS) isolate, suggesting a chromosomal location. The spe-h gene was found in only 24% of the GAS isolates and is probably located on a mobile DNA element. The smez gene displays extensive allelic variation and appears to be in linkage equilibrium with the M/emm type. 22 novel smez alleles were identified from 21 different M/emm types in addition to the already reported alleles smez and smez-2 with sequence identities between 94.5 and 99.9%. Three alleles are nonfunctional due to a single base pair deletion. The remaining 21 alleles encode distinct SMEZ variants. The mosaic structure of the smez gene suggests that this polymorphism has arisen from homologous recombination events rather than random point mutation. The recently resolved SMEZ-2 crystal structure shows that the polymorphic residues are mainly surface exposed and scattered over the entire protein. The allelic variation did not affect either Vß specificity or potency, but did result in significant antigenic differences. Neutralizing antibody responses of individual human sera against different SMEZ variants varied significantly. 98% of sera completely neutralized SMEZ-1, but only 85% neutralized SMEZ-2, a very potent variant that has not yet been found in any New Zealand isolate. SMEZ-specific Vß8 activity was found in culture supernatants of 66% of the GAS isolates, indicating a potential base for the development of a SMEZ targeting vaccine.

Key Words: superantigen, streptococcal exotoxin, multiple allelic variation, gene mosaic, antigen variation


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