The majority of the HIV vaccines under development are aimed at stimulating T cell responses. Therefore, it is critical to delineate the factors regulating the generation of the T cell responses and to develop strategies maximizing vaccine-induced T cell responses. The identification of these factors and the delineation of the kinetics of the generation of vaccine-induced immune responses have been hard to investigate, due to the limited number of precursor naive antigen-specific T cells. To overcome these obstacles, Estcourt and collaborators have developed an elegant strategy that consists of an in vivo mouse model employing transfer of naive CFSE-labeled TCR-transgenic T lymphocytes into syngeneic nontransgenic recipients prior to vaccination. Using this model, the authors demonstrate that the dose, the route of administration and the type of vaccine determine the magnitude, the dissemination and the kinetics of vaccine-induced T cell responses. Furthermore, the mouse model of Estcourt and collaborators may represent the basis for the development of powerful in vivo experimental strategies to evaluate vaccine candidates.