Recognition of leukemic blasts by HLA-DPB1-specific cytotoxic T cell clones: a perspective for adjuvant immunotherapy post-bone marrow transplantation

There is increasing evidence that the immune response plays a role in the p revention of leukemic relapses after allogeneic bone marrow transplantation (BMT), Producing this effect (referred to as the graft-versus-leukemia rea ction or GVL) is a current goal of clinical transplantation. At present, al l protocols rely on the injection of donor T cells with unknown specificiti es. In keeping with this approach, we recently proposed the use of a single allogeneic T cell clone transfected with the HSv-tk gene to target an HLA- DPB1 mismatch in the GVH direction. For this strategy to be successful, HLA -DP antigens must be expressed on leukemic cells, which should be recognise d by the HLA-DP-specific T cell clone and subsequently destroyed. In the pr esent study, differential expression of HLA-DR, -DQ and -DP was tested by f luorescence using monoclonal antibodies on a panel of 46 acute myeloid leuk emias (AML), 28 acute lymphoblastic leukemias (ALL) and 31 chronic lymphocy tic leukemias of B cell origin (B-CLL), The vast majority of leukemic cells expressed HLA-DP antigens although with considerable variability. HLA-DPB1 genotyped leukemic cells were used as target cells for an HLA-DPB1*0401-sp ecific T cell clone, Specific recognition of leukemic blasts was demonstrat ed for 11 out of 11 B-CLL, 11 out of 19 AML and nine out of 16 ALL. These d ata show that most leukemic blasts are accessible to direct lysis by alloge neic HLA-DP-specific T cells.