PREFERENTIAL USAGE OF T-CELL RECEPTOR (TCR) V-BETA BY ALLOGENEIC T-CELLS RECOGNIZING MYELOID-LEUKEMIA CELLS - IMPLICATIONS FOR SEPARATING GRAFT-VERSUS-LEUKEMIA EFFECT FROM GRAFT-VERSUS-HOST DISEASE

New understanding of the alloresponse following bone marrow transplant ation supports the possibility that the graft-versus-host disease (GVH D) response can be separated from a favorable graft-versus-leukemia (G VL) effect. We used chronic myeloid leukemia (CML) cells to generate 1 22 recipient-reactive T cell clones from a closely HLA-matched sibling responder. Clones were tested for their proliferative response to sti mulator CML cells or PHA-transformed (non-leukemic) lymphoblasts. Of 7 8 clones tested, 32 recognized both leukemia cells and PHA blasts, 19 only CML and four only PHA blasts. The remainder were non-specific res ponders. This functional specificity corresponded to distinct patterns of T cell receptor (TCR) V beta usage: clones recognizing CML cells p referentially used V beta 5, V beta 6/7 while clones recognizing both CML and PHA blasts or only PHA blasts preferentially used V beta 3 and V beta 8. It may therefore be possible to identify in vitro-generated myeloid leukemia-restricted donor T cells by their pattern of V beta usage. TCR V beta antibodies could thus be used to select and expand l eukemia-restricted donor T cells for transfusion after BMT to specific ally enhance the GVL response.