Analysis of the CDR3 region of alpha/beta T-cell receptors (TCRs) and TCR BD gene double-stranded recombination signal sequence breaks end in peripheral blood mononuclear cells of T-lineage acute lymphoblastic leukemia.

摘要

Recently, numerous reports have highlighted the restriction of the CDR3 length of T-cell receptor (TCR) beta chain in T-cells infiltrating solid tumors and hematological malignancies. However, these studies ignored the restriction of CDR3 length of TCR alpha chain and few of them attempted to reveal the mechanisms of the oligo-clonal expansion of T cells in the tumors. The primary aims of this study were twofold to: (i) analyze the CDR3 length of TCR alpha and beta chain in peripheral blood mononuclear cells of T-lineage acute lymphoblastic leukemia (T-ALL); and (ii) discover the relationship between the clonality of T cells and the process of TCR rearrangement in peripheral T cells. To this end, we investigated the TCR BV and TCR AV family spectratypes of two T-ALL patients and healthy controls using the immunoscope spectratyping technique. We found that the spectratypes exhibited a Gaussian distribution in healthy controls. However, the TCR repertoires of the two patients were highly restricted in the number of different TCR BV and TCR AV family members present. Furthermore, we found that the peripheral blood mononuclear cells (PBMC) of two T-ALL patients had the recombination signal sequence (RSS) 5'- and 3'-breaks end in the TCR BD2 gene using a specialized ligation-mediated polymerase chain reaction, implying the ongoing recombination of the TCR beta gene. Analysis of the particular CDR3 length of TCR alpha/beta T cells might be helpful for further study of the individualized therapy of T-ALL. This information will also be helpful in exploring new immunological pathogenesis and facilitating the design of a T-ALL vaccine, as well as in improving our understanding of healthy human T-cell development.