We have presented the results of studies using chimeric animals to examine the role of distinct cell subsets in shaping the TCR repertoire. Examination of specificity and TCR expression in antigen-specific long-term T-cell lines derived from these chimeras suggests that bone marrow-derived APC play a role in the selection of T cells for MHC restriction during development, and also profoundly influence the expansion of the TCR repertoire following antigen priming. An understanding of the molecular mechanisms that govern TCR repertoire maturation may await the development of effective in vitro model systems of T-cell differentiation.