The structural basis of T-cell activation by superantigens

LI, HM; LLERA, A; MALCHIODI, EL; MARIUZZA, RA

ANNUAL REVIEW OF IMMUNOLOGY

Lugar: Palo Alto, CA; 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 large fractions(5–20%) of the T cell population. Activation requires simultaneous interactionof the SAG with the V¯ domain of the T cell receptor (TCR) and with majorhistocompatibility complex(MHC)class II molecules on the surface of an antigenpresentingcell. Recent advances in knowledge of the three-dimensional structureof bacterial SAGs, and of their complexes with MHC class II molecules and theTCR ¯ chain, provide a framework for understanding the molecular basis of T cellactivation by these potent mitogens. These structures along with those of TCRpeptide/MHC complexes reveal how SAGs circumvent the normal mechanismfor T cell activation by peptide/MHC and how they stimulate T cells expressingTCR ¯ 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 ¯ chains, and for the observedinfluence of the TCR ® chain on SAG reactivity. These studies open the way tothe design of SAG variants with altered binding properties for TCR and MHC foruse as tools in dissecting structure-activity relationships in this system.