HLA compatibility in organ transplantation

The ultimate goal of transplant biologists is the induction of clinical tolerance (antigen-specific unresponsiveness), allowing the long-term survival of human allografts without the need of HLA compatibility, without continuous recipient immunosuppression, and without the concomitant risks of infection, malignancy, anduor specific drug side-effects. Several approaches to solve this problem have proved successful in animal models and are being tested in humans. Opelz and Terasaki, and their collaborators, first reported improved clinical outcome in transplant patients who received blood transfusions w1x. This seminal observation gave rise to a series of experimental protocols using blood, anduor blood products, for the induction of tolerance in animal models and in clinical practice w2x. Wood has recently reviewed the use of tolerance inducing doses of class I MHCantigens in various forms for the induction of specific unresponsiveness to alloantigens w3x. Recent studies confirm that pre-treatment with soluble, or membranebound, donor class I MHC-antigens is capable of inducing immune unresponsiveness to a subsequent organ transplant, although Pouteil-Noble et al. question whether class II MHC-antigen alone can induce specific unresponsiveness in vivo w4x. In parallel to these ‘whole molecule’ strategies of tolerance induction, the use of synthetic peptides, corresponding to class II HLA sequences, may be used for the in vitro definition of the immunogenic epitopes of the HLA antigens w5x. The epitope map of these HLA antigens will be useful in the future for induction of T cell energy anduor tolerance, overcoming probably the multiple problems from the HLA incompatibility. HLA matching in transplantation: present of history?