Oligoclonal Vβ21 with Different Vα Partner in T Cells Associated with CML Cell Antigens

Chronic myeloid leukemia (CML) is one of most common leukemia, although target therapy with imatinib is significant improved the survival rate, disease relapse and drug resistant with abl gene mutant are still the major clinical problem, improvement strategy to reverse the outcome of CML is the key point for the researchers. T-cell immunodeficiency was suggested in tumor patients for many years, understanding T cell immune status in leukemia patients might suggest treatment strategies to enhance immune competence in all. In order to investigate the clonal expansion and the feature of CDR3 sequence of T cells in patients with CML, the CDR3 of TCR Vα 29 and TCR Vβ 24 subfamily genes were amplified in peripheral blood mononuclear cells (PBMCs) from two case with CML using RT-PCR, the PCR products were further analyzed by genescan technique to evaluate clonality of the detectable TCR Vα and Vβ subfamilies. The oligoclonal PCR products were analyzed by sequencing to define the sequence of CDR3. Oligoclonal Vβ21 T cells could be identified in both CML cases, which might partner with different oligoclonal Vα subfamilies, including Vα7, Vα13 or Vα18. The CDR3 sequences from two Vβ21 and three Vα oligoclonal TCR genes were identified in Vβ21NDβNJβ1.1, Vβ21NDβNJβ2.7, Vα7NJα23, Vα13NJα49, Vα18NJα5 respectively. The length and motifs of CDR3 seem different in all five TCR genes, however, the motifs in both Vβ21 genes (GAV or LRV) share the valine as last residue of CDR3 motif, and all of three Vα gene (Vα7:G; Vα13:GDEAD or Vα18:GG ) share the Glycine as first residue in the CDR3 motif. All of five TCR sequences were already submitted to the Genbank (Accession No: EU395806, EU379940, FJ009444, EU589347 or EU770971 respectively). The results indicated that oligoclonal Vβ21 genes with different Vα partners which share part of CDR3 motifs might recognize the similar CML associated antigen epitope in CML patients. Farther investigation will be constructed the recombination vector containing the antigen specific TCRs for gene transfer to establish TCR modified-T cells, which was expected to employ for specific immunotherapy in CML.