Identification of Specific TCR Vβ3 and Vβ13 Genes Relate to Diffuse Large B-Cell Lymphoma-Associated Antigen.

Abstract

Diffuse large B-cell lymphomas (DLBL) are the most common type of non-Hodgkin's lymphoma (NHL), account for 30% to 40% of NHL. Treatment with conventional combination chemotherapy produces complete remission rates of 50 to 70%. Target therapy such as anti-CD20 monoclonal antibody (rituximab) had shown favourable results. In recent years, specific adoptive immunotherapy with tumor-specific T-cells was considered as a new and promising treatment in malignancy. Thereby, researches are focused mainly on the generation of effective antigen specific T-cells, both autologous and allogeneic specific T cells. The antigen specific T cells could be determined by analysis of the T-cell receptor (TCR) Vα or Vβ repertoire, which display monoclonal or oligoclonal expansion. In order to develop the specific cellular immunotherapy in DLBL, in the present study, we analysis at first the distribution and clonality of TCR Vβ repertoire in peripheral blood T cells by RT-PCR and genescan technique, which was expected to define the DLBL associated TCR Vβ subfamily T cells. 6 cases with DLBL were used in the study. The skew distribution and clonal expansion of TCR Vβ subfamily T cells could be found in all patients with DLBL. Monoclonal expanded T cells were identified in 3 cases, which used the Vβ3 (1 case) and Vβ13 (2 cases) subfamilies, the PCR products from the monoclonal T cells were analyzed by direct sequencing to define CDR3 sequence. The CDR3 sequences from these 3 TCRβ genes were identified, which were not identical in the reported TCR sequences in Genebank. The whole sequences of Vβ3 and Vβ13 found in 3 patients with DLBL were amplified and cloned, which are being registered in NCBI Genebank. These specific TCR Vβ genes will be farther used for research on generation of CTL by TCR gene-modified technique, and so on. In the clinical observation showed that patients who had specific reactive T cell clones had a preferable prognosis, suggesting that these detectable clonal expanded T cells might play a crucial role in tumor eradication.