Recent studies in the field of CD8⁺ Tregs have allowed a better identification and characterization of this subset of regulatory cells. Their key role in the regulation of allogeneic responses is now well established. To take full advantage of CD8⁺ Treg cells in future therapeutic applications, a better knowledge is required, particularly concerning the contribution of the T-cell receptor (TCR) in cell function as well as the role and importance of its antigenic specificity. Here, we focused on the CD8⁺CD45RC^low Tregs, which in rats induce an indefinite long-term allograft acceptance. We summarized recent findings on their interaction properties with antigen-presenting cells. Identification of the antigenic targets and TCR repertoire of CD8⁺ Tregs will allow a better understanding of their recognition properties and will highlight the potential of such of specific population in cell-based treatment.