The status of autoimmune disease therapies is not satisfactory. Antigen-specific immunotherapy has potential as a future therapy that could deliver maximal efficacy with minimal adverse effects. Several trials of antigen-specific immunotherapy have been performed, but so far no clear directions have been established. With regard to antigen-specificity in the immune system, T cells are essential components. However, at present, we do not have a sufficient range of strategies for manipulating antigen-specific T cells. In this review, the authors propose that T cell receptor gene transfer could be used for antigen-specific immunotherapy. In the proposed technique, important disease-related and, thus, antigen-specific T cells in patients would first be identified, and then a pair of cDNAs encoding alpha and beta T cell receptors would be isolated from these single T cells. These genes would then be transferred into self lymphocytes. These engineered antigen-specific cells can also be manipulated to express appropriate functional genes that could then be applied to specific immunotherapy.