Functional characterization of the interaction between the superantigen staphylococcal enterotoxin A and the TCR.
In this report, we show that despite an overall amino acid residue identity of more than 80% between the staphylococcal enterotoxins (SE) A and E, these proteins markedly differ in their absolute requirement for the MHC class II during T cell activation. The superantigens were produced as C215Fab-SE fusion proteins and analyzed for their ability to activate T cells in a MHC class II-independent manner, using C215 Ag expressing cell lines as pseudo super-APCs. C215Fab-SEA, but not C215Fab-SEE, induced T cell cytotoxicity and proliferation in these MHC class II-independent systems. Introduction of a region from SEA, comprising amino acids 20-27, to SEE transferred the ability to engage T cells in the absence of MHC class II. Analysis of the Vbeta specificity of the chimeric SEA/SEE molecules and a panel of SEA mutants demonstrated that the site for TCR interaction covers the edge surrounding the shallow cavity on top of the SEA molecule.
Antonsson
P
P
Pharmacia and Upjohn, Lund Research Center, Sweden. per.antonsson@eu.pnu.com
Wingren
A G
AG
Hansson
J
J
Kalland
T
T
Varga
M
M
Dohlsten
M
M
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000737:chemistry*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D018089:Superantigens; C049463:enterotoxin E, Staphylococcal; C026066:enterotoxin A, Staphylococcal