Tolerance to maternal immunoglobulins: Resilience of the specific T cell repertoire in spite of long-lasting perturbations

T cell tolerance is established and maintained through various mechanisms, the critical component being the persistence of the specific Ag, However, a t the molecular level, the nature of the recovering TCR repertoire followin g breakdown of tolerance is unknown, We address this important question by following kappa light chain constant region (C kappa)-specific CD4(+) T cel ls of K light chain knock-out (kappa(-/-)) mice born to kappa(+/-) mothers. These cells, which were in contact with maternal kappa(+) Igs from early o ntogeny until weaning, were strongly tolerized, Tolerance was reversible an d waned with the disappearance of peptide C kappa(134-148) presentation in lymphoid organs, including the thymus, Whereas three specific VP-JP rearran gements emerged in the peptide C kappa(134-148)(-) specific CD4(+) T cell r esponse of all regular kappa(-/-) mice, soon after breakdown of tolerance o nly one of these rearrangements was detected. The two others displayed a si gnificant delay in reappearance and were still rare at 26 wk of age, while the control proliferative response had already recovered 3 mo earlier. At 5 2 wk of age, a complete recovery of the three canonical V beta-J beta rearr angements was observed. Thus, although profoundly perturbed for several mon ths, the T cell repertoire returns to equilibrium, highlighting the resilie nt nature of this system.