Ontogeny of cytotoxic T-cell repertoire modification.

The specificity of the residual anti-B10 cytotoxic T-cell response of B10. A mice rendered neonatally tolerant of B10 was compared to the anti-B10 response of adult and neonatal normal B10. A mice. The response of both spleen cells and thymus cells from adult and neonatal normal mice was biased toward Kb. This was in contrast to the response from tolerant spleen which was biased toward Db. The results suggest that the repertoire of normal mice is established neonatally and does not change radically without specific antigenic challenge. Furthermore the fact that the residual tolerogen specific cytotoxic T-cell precursors (pTc) in tolerant mice have a different repertoire to normal neonates makes it unlikely that they are remnants of a neonatal repertoire that developed prior to the full establishment of tolerance. Taking into account the present and previous results, the residual tolerogen-specific Tc in tolerant mice most likely represent a population of cells that has escaped tolerance induction due to their low avidity for antigen and provide the first evidence that avidity plays a role in tolerance among cytotoxic T cells.