NEOPLASIA Leukemia-associated monoclonal and oligoclonal TCR-BV use in patients with B-cell chronic lymphocytic leukemia

T-cell receptor–B-variable (TCR-BV)geneus-age and the CDR3 size distribution pattern were analyzed by reverse transcription– polymerase chain reaction (RT-PCR) in pa-tients with B-cell chronic lymphocytic leuke-mia (B-CLL) to assess the T-cell repertoire. The use of TCR-BV families in CD4 and CD8 T cells stimulated with autologous activated leukemic cells was compared with that of freshly obtained blood T cells. Overexpres-sionof individualTCR-BVfamilieswas found in freshly isolated CD4 and CD8 T cells. Polyclonal, oligoclonal, and monoclonal TCR-CDR3 patterns were seen within such overexpressed native CD4 and CD8 TCR-BV families. In nonoverexpressed TCR-BV fami-lies, monoclonal and oligoclonal popula-tions were noted only within the CD8 sub-set. After in vitro stimulation of T cells with autologous leukemic B cells, analyses of the CDR3 length patterns showed that in expanded TCR-BV populations, polyclonal patterns frequently shifted toward a mono-clonal/oligoclonal profile, whereas largely monoclonal patterns in native overex-pressed TCR-BV subsets remained mono-clonal. Seventy-five percent of CD8 expan-sions found in freshly obtained CD8 T cells further expanded on in vitro stimulation with autologous leukemic B cells. This suggests a memory status of such cells. In contrast, the unusually high frequency of CD4 T-cell expansions found in freshly isolated periph-eral blood cells did not correlate positively to in vitro stimulation as only 1 of 9 expan-sions continued to expand. Our data sug-gest that leukemiacell–specificmemoryCD4 and CD8 T cells are present in vivo of patients with CLL and that several leukemia cell–associatedantigens/epitopesare recog-nized by the patients ’ immune system, indi-cating that whole leukemia cells might be of preference for vaccine development. (Blood