HLA CLASS-II RESTRICTED T-CELL REACTIVITY TO A DEVELOPMENTALLY-REGULATED ANTIGEN SHARED BY LEUKEMIC-CELLS AND CD34(+) EARLY PROGENITOR CELLS

After allogeneic bone marrow transplantation (BMT), the beneficial gra ft-versus-leukemia (GVL) effect but also the life-threatening graft-ve rsus-host disease (GVHD) are mediated by T cells of the grafted marrow . The identification of leukemia cell-reactive T cells and their ligan ds are, therefore, crucial for the development of new anti leukemia st rategies. Here we describe a leukemia-reactive allo-HLA class II restr icted CD4(+) T-cell clone, 6.2, isolated from a healthy individual aft er stimulation with allogeneic leukemic cells. Clone 6.2 recognizes le ukemic cells from several AML patients without showing reactivity to u nfractioned peripheral blood mononuclear cells, monocytes, B cells, T- cell blasts, and proximal tubulus epithelial cells. Interestingly, clo ne 6.2 also recognizes BM cells derived from healthy individuals and i nhibits the colony formation of myeloid and erythroid cell lineages. I n the BM, clone 6.2 recognizes only CD34(+) early precursor cells but not CD34(-), more differentiated cells. Thus, the target antigen of cl one 6.2 is developmentally regulated and expressed only by leukemic ce lls and CD34(+) early progenitor cells in the hematopoietic system. We suggest that targeting the T-cell immune response to leukemia-associa ted, developmentally regulated antigens of the hematopoietic system ca n provide a basis for the separation of GVL from GVHD, and may lead to new therapeutic approaches for residual and relapsed leukemia. (C) 19 97 by The American Society of Hematology.