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J. Exp. Med.,
Volume 189, Number 2, January 18, 1999 253-264
By
From the * Basel Institute for Immunology, 4005 Basel, Switzerland; and the Antagonist peptides inhibit T cell responses by an unknown mechanism. By coexpressing two
independent T cell receptors (TCRs) on a single T cell hybridoma, we addressed the question
of whether antagonist ligands induce a dominant-negative signal that inhibits the function of a
second, independent TCR. The two receptors, V Department of
Pathology and Immunology, Monash Medical School, Prahran, Victoria 3181, Australia
2V
5 and V2V10, restricted by H-2Kb
and specific for the octameric peptides SIINFEKL and SSIEFARL, respectively, were coexpressed on the same cell. Agonist stimulation demonstrated that the two receptors behaved independently with regard to antigen-induced TCR downregulation and intracellular biochemical signaling. The exposure of one TCR (V2V5) to antagonist peptides could not inhibit a
second independent TCR (V2V10) from responding to its antigen. Thus, our data clearly
demonstrate that these antagonist ligands do not generate a dominant-negative signal which affects the responsiveness of the entire cell. In addition, a kinetic analysis showed that even 12 h
after engagement with their cognate antigen and 10 h after reaching a steady-state of TCR internalization, T cells were fully inhibited by the addition of antagonist peptides. The window
of susceptibility to antagonist ligands correlated exactly with the time required for the responding T cells to commit to interleukin 2 production. The data support a model where antagonist
ligands can competitively inhibit antigenic peptides from productively engaging the TCR.
This competitive inhibition is effective during the entire commitment period, where sustained
TCR engagement is essential for full T cell activation.
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