Cutting edge: trimolecular interaction of TCR with MHC class II and bacterial superantigen shows a similar affinity to MHC:peptide ligands.
Bacterial superantigens such as Staphylococcus aureus enterotoxin A (SEA) are very potent stimulators of T cells. They bind to the Vbeta region of the TCR and to MHC class II, stimulating T cells at nanomolar concentrations. Using surface plasmon resonance measurements, we find that binding between the individual components of the complex (TCR-class II, TCR-SEA, SEA-class II) is very weak, but that the stability of the trimolecular complex is considerably enhanced, reaching an affinity similar to that found for TCR interactions with MHC:peptide ligand. Thus, the potency of SEA in stimulation of T cells is not due to particularly strong affinities between the proteins, but to a cooperative effect of interactions in the TCR-SEA-MHC class II trimolecular complex that brings the kinetics into a similar range to binding of conventional Ags. This range may be the optimum for T cell activation.
Redpath
S
S
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Alam
S M
SM
Lin
C M
CM
O'Rourke
A M
AM
Gascoigne
N R
NR
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D015703:Antigens, CD; D001704:Biopolymers / Q000276:immunology / Q000378:metabolism; D010856:Columbidae / Q000276:immunology; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D019281:Dimerization; D004768:Enterotoxins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D012995:Solubility; D018089:Superantigens / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D000942:Antigens, Bacterial; D015703:Antigens, CD; D001704:Biopolymers; C490007:Cd244a protein, mouse; D003574:Cytochrome c Group; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal