• allorecognition;
  • human leucocyte antigen;
  • T cell;
  • tolerance;
  • tumour immunotherapy

Although the T-cell response to allogeneic cells is typically regarded as a detrimental phenomenon responsible for rejection of transplanted allografts and graft-vs.-host disease following haematopoietic stem cell transplantation, beneficial components also exist within the alloreactive population. Alloreactive T cells specific for tumour antigens can contribute to the elimination of malignant cells, and alloantigen-specific regulatory T cells can promote transplant tolerance. The challenge is to separate the good from the bad. We review how the identification, isolation and manipulation of beneficial alloreactive T cells has grown from a greater understanding of the molecular basis of the T-cell alloresponse and how alloaggression could be exploited for immunotherapy.