Identification of Idiotype TCR Vα6, Vα10 and Vβ23 Relate to APL-Associated Antigen

Abstract

Differentiation therapy with all-trans retinoic acid in combination with chemotherapy has significantly improved survival in patient with acute promyelocytic leukaemia (APL). However, relapse remains a major problem. In recent years, specific adoptive immunotherapy with tumor-specific T-cells was considered as a new approach to malignancy therapy. Recently, researches are focus on searching the generation of effective tumor antigen specific T-cells. The tumor antigen specific T cells could be determined by analysis of the T-cell receptor (TCR) Vα or Vβ repertoire, which display monoclonal or oligoclonal pattern. In order to develop the specific cellular immunotherapy in APL, in this present study, we analysis the clonality and the pattern of CDR3 sequence of TCR Vα and Vβ repertoire in peripheral blood T cells by RT-PCR and genescan technique, which was expected to define the APL associated TCR Vα or Vβ subfamily T cells. Oligoclonal T cells expressed TCR Vα6, Vα10 or Vβ23 genes were identified from one APL patient. The molecular characteristics of the CDR3 of Vα and Vβ genes rearrangement were Vα6-N-Jα17, Vα10-N-Jα35 and Vβ23-N-Dβ1-NJβ2.7. And the amino acid sequence of CDR3 region in TCR Vα6, Vα10 and Vβ23 subfamilies were CAMRENSAGNK, YLCAGDELLWECA or CASSSKWAGGTYEQY, respectively. These sequences were accepted by GenBank (Accession Number EU544946, EU544947 and EU647219). In conclusions, three idiotype Vα and Vβ sequences were identified in a case with APL, which was thought that may mediate the host specific immunity response for leukemia cells in APL. Farther investigation will be performed on construction the vector containing the antigen specific TCRs for gene transfer to establish TCR modified-T cells for specific immunotherapy of APL.