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Phosphorylation Is Not Required for the Induction of T Cell Antagonism by Altered Peptide Ligands1
*
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105; and
Graduate Program in Pathology and
Department of Pathology, University of Tennessee Medical Center, Memphis, TN 38163
T cells recognize foreign Ags in the form of short peptides bound
to MHC molecules. Ligation of the TCR:CD3 complex gives rise to the
generation of two tyrosine-phosphorylated forms of the CD3 
-chain,
pp21 and pp23. Replacement of residues in MHC-bound peptides that alter
its recognition by the TCR can generate altered peptide ligands (APL)
that antagonize T cell responses to the original agonist peptide,
leading to altered T cell function and anergy. This biological process
has been linked to differential CD3 phosphorylation and generation
of only the pp21 phospho-species. Here, we show that T cells expressing
CD3 mutants, which cannot be phosphorylated, exhibit a 5-fold
reduction in IL-2 production and a 30-fold reduction in sensitivity
following stimulation with an agonist peptide. However, these T cells
are still strongly antagonized by APL. These data demonstrate that: 1)
the threshold required for an APL to block a response is much lower
than for an agonist peptide to induce a response, 2) CD3 is required
for full agonist but not antagonist responses, and 3) differential
CD3 phosphorylation is not a prerequisite for T cell
antagonism.
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