Superantigenos

CLINICAL MICROBIOLOGY REVIEWS, July 1995, p. 411–426 0893-8512/95/$04.00 0 Copyright 1995, American Society for Microbiology

Vol. 8, No. 3

Bacterial Pyrogenic Exotoxins as Superantigens
MALAK KOTB* Departments of Surgery, Microbiology and Immunology, University of Tennessee, and Veteran’s Affairs Medical Center, Memphis, Tennessee INTRODUCTION.......................................................................................................................................................411 SUPERANTIGENS: DEFINITION AND MECHANISM OF IMMUNE STIMULATION ..............................411 PRACTICAL CONSIDERATIONS IN ASSIGNING SUPERANTIGENIC PROPERTIES .............................413 BACTERIAL PYROGENIC EXOTOXINS AS SUPERANTIGENS....................................................................413 STRUCTURAL FEATURES OF SECRETED PYROGENIC SUPERANTIGENS ............................................414 FUNCTIONAL DOMAINS WITHIN THE PYROGENIC SUPERANTIGENS IMPORTANT FOR THEIR INTERACTION WITH MHC CLASS II MOLECULES AND TCR ...........................................................414 POSSIBLE FATE OF T CELLS THAT ENCOUNTER SUPERANTIGEN IN VIVO......................................415 PYROGENIC SUPERANTIGENS AS MEDIATORS OF HUMAN DISEASES................................................415 Food Poisoning........................................................................................................................................................416 Superantigen-Mediated Toxic ShockSyndrome.................................................................................................416 Superantigens and Autoimmunity ........................................................................................................................418 Other Human Diseases That May Be Linked to Bacterial Pyrogenic Superantigens ..................................419 THERAPEUTIC STRATEGIES IN SUPERANTIGEN-ASSOCIATED DISEASES..........................................419 PYROGENIC SUPERANTIGENS AS CURES FOR HUMAN DISEASES........................................................420 WHY DO BACTERIA PRODUCE SUPERANTIGENS?.......................................................................................420 CONCLUDING REMARKS......................................................................................................................................421 REFERENCES ............................................................................................................................................................421 INTRODUCTION In recent years, a great deal of new knowledge about a group of microbial proteins known as superantigens has been generated. These molecules have elicited tremendous interest because they interact with theimmune system in a nonconventional manner and can potentially trigger diseases such as toxic shock, food poisoning, and autoimmunity. Realizing the immunological and biological effects of superantigens has helped to discern the mechanism of pathogenesis of a number of diseases linked to microbial infections and has offered new possibilities for the development of novel and effective therapeuticstrategies. Knowledge gained from studying the interaction of superantigens with cells of the immune system has illuminated many aspects of immune regulation and signal transduction via the T-cell receptor (TCR) and major histocompatibility complex (MHC) class II molecules. In addition, scientists were quick to exploit certain features of superantigens in developing novel immunotherapeutic strategies foruse in cancer therapy. As a result, superantigens have attracted scientists from diverse disciplines to investigate various aspects of these fascinating molecules. This amalgamation of expertise has contributed tremendously to our knowledge of the immune system and our understanding of the pathogenesis of many human diseases. Superantigens can be produced by viruses and bacteria, including...