In vitro T-cell receptor V beta repertoire analysis may identify which T-cell V beta families mediate graft-versus-leukaemia and graft-versus-host responses after human leucocyte antigen-matched sibling stem cell transplantation

We studied oligoclonal T-cell expansions of 24 T-cell receptor (TCR) V beta families in normal donor lymphocytes stimulated with patient's cells and i n recipient blood after transplant, using a polymerase chain reaction-based assay (spectratyping). T cells from donor blood were incubated with separa ted myeloid leukaemia cells or T cells from the HLA-identical sibling recip ient. In five of the six patients tested, the T-cell V beta skewing pattern observed in vitro was seen in vivo after transplant. After transplant, the myeloid-specific V beta skewing coincided with the disappearance of residu al disease in three patients and in one patient skewing was lost at the tim e of leukaemic relapse. In functional tests, T cells generated against leuk aemic cells in vitro produced interferon gamma in response to the leukaemia . Removal of the leukaemia-expanded skewed V beta families significantly de creased cytotoxic killing of the leukaemia. However, while there was a gene ral concordance in the V beta family exhibiting clonal expansion in vitro a nd in vivo, the exact clonotype expanded in vitro and in vivo differed. The se findings suggest that alloresponses involve multiple T-cell clones withi n a restricted TCR V beta repertoire that undergo different selection press ures in vitro and in vivo.