Preferential usage of T cell receptor (TCR) V β by allogeneic T cells recognizing myeloid leukemia cells: implications for separating graft-versus-leukemia effect from graft-versus-host disease

Abstract

New understanding of the alloresponse following bone marrow transplantation supports the possibility that the graft-versus-host disease (GVHD) response can be separated from a favorable graft-versus-leukemia (GVL) effect. We used chronic myeloid leukemia (CML) cells to generate 122 recipient-reactive T cell clones from a closely HLA-matched sibling responder. Clones were tested for their proliferative response to stimulator CML cells or PHA-transformed (non-leukemic) lymphoblasts. Of 78 clones tested, 32 recognized both leukemia cells and PHA blasts, 19 only CML and four only PHA blasts. The remainder were non-specific responders. This functional specificity corresponded to distinct patterns of T cell receptor (TCR) Vβ usage: clones recognizing CML cells preferentially used Vβ 5, Vβ 6/7 while clones recognizing both CML and PHA blasts or only PHA blasts preferentially used Vβ 3 and V β 8. It may therefore be possible to identify in vitro-generated myeloid leukemia-restricted donor T cells by their pattern of Vβ usage. TCR Vβ antibodies could thus be used to select and expand leukemia-restricted donor T cells for transfusion after BMT to specifically enhance the GVL response.