Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes.

MCCORMICK, JOHN K; TRIPP, TIMOTHY J; LLERA, ANDREA S; SUNDBERG, ERIC J; DINGES, MARTIN M; MARIUZZA, RA; SCHLIEVERT, PM; ANDREA SABINA LLERA

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda, MD; Año: 2003 vol. 171 p. 1385 - 1392

0022-1767

Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHCclass II molecules on APCs and with particular variable regions of the TCR b-chain (Vb). To further define the interface betweenthe bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within theputative TCR binding region of TSST-1 along the central a helix adjacent to the N-terminal a helix and the a7-a9 loop as wellas with two universally conserved SAG residues (Leu137 and Tyr144 in TSST-1). Mutants were analyzed for multiple functionalactivities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues(Gly16, Trp116, Glu132, His135, Gln136, and Gln139), each individually critical for functional activity as well as direct interaction withthe human TCR Vb2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, amodel of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3loop of Vb2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vb specificity ofTSST-1.