The T cell receptor beta-chain second complementarity determining region loop (CDR2beta governs T cell activation and Vbeta specificity by bacterial superantigens.

ABSTRACT: Superantigens (SAgs) are microbial toxins defined by their ability to activate T lymphocytes in a T cell receptor (TCR) ?-chain variable domain (V?)-specific manner. Although existing structural information indicates that diverse bacterial SAgs all uniformly engage the V? second complementarity determining region (CDR2?) loop, the molecular rules that dictate SAg-mediated T cell activation and V? specificity are not fully understood. Herein we report the crystal structure of human V?2.1 (hV?2.1) in complex with the toxic shock syndrome toxin-1 (TSST-1) SAg, and mutagenesis of hV?2.1 indicates that the non-canonical length of CDR2? is a critical determinant for recognition by TSST-1 as well as the distantly related SAg streptococcal pyrogenic exotoxin C. Frame work (FR) region 3 is uniquely critical for TSST-1 function explaining the fine V?-specificity exhibited by this SAg. Furthermore, domain swapping experiments with SAgs, which use distinct domains to engage both CDR2? and FR3/4? revealed that the CDR2? contacts dictate T lymphocyte V?-specificity. These findings demonstrate that the TCR CDR2? loop is the critical determinant for functional recognition and V?-specificity by diverse bacterial SAgs.

SUBMITTER: Nur-ur Rahman AK 

PROVIDER: S-EPMC3039367 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature