The highly alloreactive nature of dual TCR T cells

T cells can mediate allograft rejection and graft-versus-host disease (GVHD), but are necessary for tolerance and protective immunity. Identifying T-cell populations differentially responsible for these effects has been a goal in transplant research. This review describes investigation of a small subset of T cells naturally predisposed toward alloreactivity, cells expressing two T-cell receptors (TCRs).

Rare peripheral T cells express two αβTCRs. Their impact on T-cell development and function has been uncertain. Recent work demonstrates an important role for these cells in mouse models and human hematopoietic stem cell transplant patients with acute GVHD. Dual receptor T cells are preferentially activated and expanded in vitro and in vivo by allogeneic stimulation. Genetic elimination of dual TCR expression results in loss of approximately half of the alloreactive repertoire and impedes the earliest steps of GVHD.

Identification of dual TCR T cells as predisposed to alloreactivity provides an opportunity to examine responses limiting transplantation. Continued investigation will reveal significant fundamental features of T-cell alloreactivity and important information about the earliest events determining allograft rejection and self-tolerance.