Targeting B cell leukemia with highly specific allogeneic T cells with a public recognition motif.

The possibility that allogeneic T cells may be targeted to leukemia has important therapeutic implications. As most tumor antigens represent self-proteins, high-avidity tumor-specific T cells are largely deleted from the repertoire of the patient. In contrast, T cells from major histocompatibility complex (MHC)-mismatched donors provide naïve repertoires wherein such cells have not been systematically eliminated. Yet, evidence for peptide degeneracy or poly-specificity warrants caution in the use of foreign human leukocyte antigen (HLA) or peptide complexes as therapeutic targets. Here, we cocultured HLA-A(*)0201-negative T cells with autologous dendritic cells engineered to present HLA-A(*)0201 complexed with a peptide from the B cell antigen CD20 (CD20p). HLA-A(*)0201/CD20p pentamer-reactive CD8(+) T cells were readily obtained from all donors. The polyclonal cells showed exquisite peptide and MHC specificity, and efficiently killed HLA-A(*)0201-positive B cells, including primary chronic lymphocytic leukemia cells. The T cell receptor (TCR) sequences displayed a novel type of conservation, with extensive homology in the TCR ß chain complementarity-determining region 3 and in J, but not V, region. This is surprising, as the donors were HLA disparate and their TCR repertoires are expected to show little overlap. The results demonstrate the first public recognition motif for an allogeneic HLA/peptide complex. The allo-restricted T cells or TCRs could provide graft-versus-leukemia in the absence of graft-versus-host disease.

Typing of European strains of parvovirus B19 by restriction endonuclease analyses and sequencing: identification of evolutionary lineages and evidence of recombination of markers from different lineages.

European isolates of parvovirus B19 were analyzed by restriction enzyme analysis of PCR products of the VP1/2 coding region and sequencing of the same amplified region, five cloned fragments from each PCR product. Two main groupings were found based on three perfectly linked point deviations. On the assumption that identical point deviations causing the various restriction patterns regardless of time and origin of virus isolation were unlikely to emerge independently in different evolutionary lineages, traits of evolutionary lineages were identified, suggesting a clonal population structure of global circulating B19 strains. However, combinations of markers from different evolutionary lineages were also found, particularly in a strain derived from an individual chronically infected with B19 for more than 7 years. As chronically infected individuals might be subject to superinfections due to contacts or possibly due to blood transfusions or the administration of gamma-globulin, it is suggested that coexistence of, and recombination between variants of B19 of different phylogenetic origin incidentally occur in such individuals.