Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens.
Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3 (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands. Comparable studies using anti-TCR antibodies of known affinity confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength.
Andersen
P S
PS
Institute for Medical Microbiology and Immunology, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen, Denmark. psa@immi.ku.dk
Geisler
C
C
Buus
S
S
Mariuzza
R A
RA
Karjalainen
K
K
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D004768:Enterotoxins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors
D000942:Antigens, Bacterial; D004768:Enterotoxins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; C034959:enterotoxin C, staphylococcal