C. Bouneaud et al., Impact of negative selection on the T cell repertoire reactive to a self-peptide: A large fraction of T cell clones escapes clonal deletion, IMMUNITY, 13(6), 2000, pp. 829-840
How negative selection shapes a polyclonal population of self-reactive T ce
lls has been difficult to address directly because of the lack of means to
isolate T cells reactive to a particular self-peptide. Here, using mice tra
nsgenic for the TCR-P chain of a CTL clone directed against a mate-specific
peptide, we compared the preimmune repertoire reactive to this peptide in
male and female animals. Surprisingly, in the presence of the deleting liga
nd, as many as 25%-40% of reactive T cells escaped clonal deletion. A corre
lation was found between T cell avidity, TCR alpha structures, and suscepti
bility to negative selection. These results suggest that numerous low-affin
ity self-specific T cells persist in the periphery and show that a deleting
ligand can specifically narrow the structural diversity of the TCR reperto
ire.