The T cell receptor beta-chain second complementarity determining region loop (CDR2beta governs T cell activation and Vbeta specificity by bacterial superantigens.
Superantigens (SAgs) are microbial toxins defined by their ability to activate T lymphocytes in a T cell receptor (TCR) β-chain variable domain (Vβ)-specific manner. Although existing structural information indicates that diverse bacterial SAgs all uniformly engage the Vβ second complementarity determining region (CDR2β) loop, the molecular rules that dictate SAg-mediated T cell activation and Vβ specificity are not fully understood. Herein we report the crystal structure of human Vβ2.1 (hVβ2.1) in complex with the toxic shock syndrome toxin-1 (TSST-1) SAg, and mutagenesis of hVβ2.1 indicates that the non-canonical length of CDR2β 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 Vβ-specificity exhibited by this SAg. Furthermore, domain swapping experiments with SAgs, which use distinct domains to engage both CDR2β and FR3/4β revealed that the CDR2β contacts dictate T lymphocyte Vβ-specificity. These findings demonstrate that the TCR CDR2β loop is the critical determinant for functional recognition and Vβ-specificity by diverse bacterial SAgs.
Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
A K M
AK
Nur-ur Rahman
Daniel A
DA
Bonsor
Christine A
CA
Herfst
Fraser
F
Pollard
Michael
M
Peirce
Aaron W
AW
Wyatt
Katherine J
KJ
Kasper
Joaquín
J
Madrenas
Eric J
EJ
Sundberg
John K
JK
McCormick
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D005098:Exotoxins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D016296:Mutagenesis; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D022801:Complementarity Determining Regions; D004768:Enterotoxins; D005098:Exotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C027951:erythrogenic toxin