The recognition of peptide variants by the T cell receptor (TCR) has r
evealed a wide range of possible responses. Here, using a series of CD
4(+) and CD4(-) variants of the same T cell hybridoma, we find that wh
ile the expression of CD4 converts weak agonists into full agonists, n
one of the antagonist peptides are efficiently recognized as agonists.
Furthermore, in antagonist assays, little difference can be seen in t
he response of CD4(+) and CD4(-) T cells. Together with previous work
showing a marked difference in stability between TCR binding to agonis
t versus antagonist ligands, these data suggest that CD4 engagement oc
curs after a TCR-peptide/MHC complex has formed and that it requires a
certain minimal half-life of the ternary complex to be fully engaged
in signaling.