The structural basis of T cell activation by superantigens.

LI H, LLERA A, MALCHIODI EL, MARIUZZA RA

ANNUAL REVIEW OF IMMUNOLOGY

Año: 1999 vol. 17 p. 435 - 466

0732-0582

Superantigens (SAGs) are a class of immunostimulatory and disease-causingproteins of bacterial or viral origin with the ability to activate largefractions (5-20%) of the T cell population. Activation requires simultaneousinteraction of the SAG with the V beta domain of the T cell receptor (TCR) andwith major histocompatibility complex (MHC) class II molecules on the surface of an antigen-presenting cell. Recent advances in knowledge of the three-dimensionalstructure of bacterial SAGs, and of their complexes with MHC class II moleculesand the TCR beta chain, provide a framework for understanding the molecular basisof T cell activation by these potent mitogens. These structures along with those of TCR-peptide/MHC complexes reveal how SAGs circumvent the normal mechanism for T cell activation by peptide/MHC and how they stimulate T cells expressing TCRbeta chains from a number of different families, resulting in polyclonal T cellactivation. The crystal structures also provide insights into the basis for thespecificity of different SAGs for particular TCR beta chains, and for theobserved influence of the TCR alpha chain on SAG reactivity. These studies openthe way to the design of SAG variants with altered binding properties for TCR andMHC for use as tools in dissecting structure-activity relationships in thissystem.