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 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.
Bouneaud
C
C
Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France.
Kourilsky
P
P
Bousso
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D018076:DNA, Complementary; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D018076:DNA, Complementary; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta