TY - JOUR
T1 - Inhibition or activation of human t cell receptor transfectants is controlled by defined, soluble antigen arrays
AU - Symer, David E.
AU - Dintzis, Renee Z
AU - Diamond, Don J.
AU - Dintzis, Howard M.
PY - 1992/11/1
Y1 - 1992/11/1
N2 - We present evidence that direct T cell receptor (TCR) occupancy by antigen can either activate or inhibit T cells, depending upon whether or not a threshold number oflocal TCRs are crosslinked by multivalent arrays of the antigen. Variants of Jurkat cells were previously transfected with TCR a and (3 chains that bind fluorescein, yielding FLTCR+ human T cells. The transfectants are activated upon binding soluble multivalent antigen arrays at concentrations well below those required for monovalent interactions. This activation, measured by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior binding avidity of multivalent ligands. Smaller, less multivalent arrays do not activate the cells, but antagonize larger arrays, demonstrating that antigen can bind TCR as either agonist or antagonist. The balance between activation and inhibition depends upon antigen array size, ligand valence, and concentration, indicating that a threshold extent of receptor crosslinking, and not individual perturbations of single TCR, is required for activation by antigen. Approximately 100 stimulatory arrays specifically bind per FLTCR+ cell at concentrations where IL-2 production is half-maximal.
AB - We present evidence that direct T cell receptor (TCR) occupancy by antigen can either activate or inhibit T cells, depending upon whether or not a threshold number oflocal TCRs are crosslinked by multivalent arrays of the antigen. Variants of Jurkat cells were previously transfected with TCR a and (3 chains that bind fluorescein, yielding FLTCR+ human T cells. The transfectants are activated upon binding soluble multivalent antigen arrays at concentrations well below those required for monovalent interactions. This activation, measured by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior binding avidity of multivalent ligands. Smaller, less multivalent arrays do not activate the cells, but antagonize larger arrays, demonstrating that antigen can bind TCR as either agonist or antagonist. The balance between activation and inhibition depends upon antigen array size, ligand valence, and concentration, indicating that a threshold extent of receptor crosslinking, and not individual perturbations of single TCR, is required for activation by antigen. Approximately 100 stimulatory arrays specifically bind per FLTCR+ cell at concentrations where IL-2 production is half-maximal.
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U2 - 10.1084/jem.176.5.1421
DO - 10.1084/jem.176.5.1421
M3 - Article
C2 - 1402685
AN - SCOPUS:0026781186
VL - 176
SP - 1421
EP - 1430
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 5
ER -