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Immunity. 2000 Dec;13(6):829-40.

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

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Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France.


How negative selection shapes a polyclonal population of self-reactive T cells 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 transgenic for the TCR-beta chain of a CTL clone directed against a male-specific peptide, we compared the preimmune repertoire reactive to this peptide in male and female animals. Surprisingly, in the presence of the deleting ligand, as many as 25%-40% of reactive T cells escaped clonal deletion. A correlation was found between T cell avidity, TCRalpha structures, and susceptibility to negative selection. These results suggest that numerous low-affinity self-specific T cells persist in the periphery and show that a deleting ligand can specifically narrow the structural diversity of the TCR repertoire.

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