Impact of negative selection on the T cell repertoire reactive to a self-peptide: A large fraction of T cell clones escapes clonal deletion

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.