INDIRECT RECOGNITION OF DONOR MHC CLASS-II ANTIGENS IN HUMAN TRANSPLANTATION

To investigate the role of the indirect pathway of recognition in huma n allograft rejection, we have mapped the dominant T cell determinant of the HLA-DR beta 10101 molecule presented by the DR beta 1*1101 ant igen. A synthetic peptide (pp 22-35) corresponding to the sequence of the dominant peptide determinant was used for testing the frequency of in vivo activated T cells in the graft and in the periphery. DR beta 11101-positive patients carrying a heart allograft mismatched for the HLA-DR1 antigen showed no reactivity to pp 22-35 during quiescence. H owever, interleukin-a-responsive T cells, which were pp 22-35 specific , were found in the circulation prior to and at the time of acute and chronic rejection. The response of in vivo and in vitro activated T ce lls was inhibited at high concentrations of peptide 22-35. This data s uggests that indirect recognition plays an important role in allograft rejection and that it can be abolished by high zone tolerance inducti on. (C) 1996 academic Press, Inc.