DURING positive selection, developing thymocytes are rescued from prog
rammed cell death by T-cell receptor (TCR)-mediated recognition of maj
or histocompatibility complex (MHC) molecules(1-3). MHC-bound peptides
contribute to this process(4-8). Recently we identified individual MH
C-binding peptides which can induce positive selection of a single TCR
(9). Here we examine peptide fine specificity in positive selection. T
hese data suggest that a direct TCR-peptide interaction occurs during
this event, and strengthens the correlation between selecting peptides
and TCR antagonists(9,10). Certain positively selecting peptides are
weakly antigenic(9). We demonstrate that thymocytes 'educated' on such
a peptide are specifically non-responsive to it and have decreased CD
8 expression levels. Similar reduction of CD8 expression on mature T c
ells converts a TCR agonist into a TCR antagonist. These data indicate
that thymocytes may maintain self-tolerance towards a positively sele
cting ligand by regulating co-receptor expression.