Characterization of CDR3 Structure of Vβ21 T Cell Clones In Patients with P210BCR-ABL Positive CML and B-ALL

Abstract

AbstractAbstract 4455The clonally expanded T cells identified in most cancer patients which were considered to respond to tumour association antigen (TAA) have definitely specific anti-tumor cytotoxicity. P210BCR-ABL protein regards as the hallmark of CML and known to be causative of the disease, and also expresses in partial acute lymphoblastic leukaemia (ALL) can induce to yield tumor-specific cytotoxic T lymphocytes (CTL) which can kill bar-abl+ tumor cells in many trials. In our previous study, we found the oligoclonal expansion of TCR Vβ21 subfamily in the peripheral blood (PB) of 8 cases with P210BCR-ABL positive CML and 3 cases with P210BCR-ABL positive B-ALL patients and 1 case with P210BCR-ABL negative B-ALL patients using the genescan technology. To further elucidate the oligoclonal TCR Vβ21 features, we carried out sequencing analysis of CDR3 region of each oligoclonal TCR Vβ21 and determined the primary structure of the CDR3 region. The 12 TCR Vβ21 clones used different Jβ segments, Jβ2.3 segment was used in 4 clones, both Jβ2.1 and Jβ1.1 segments were used in 2 clones respectively, Jβ1.2, Jβ1.3, Jβ2.2 and Jβ2.7 segments were used in 1 clone. Only a conserved amino acid motif (SLxxV) was found within the CDR3 region from 3 patients with CML. Then we constructed the three-dimensional structures of the CDR3 sequences from all 12 clones by homology modeling methods and through pairwise comparing with the three-dimensional structures of all CDR3 sequences, the results showed that the conformation of the CDR3 region either containing the conserved amino acid motif or using the same Jβ segment displayed low similarity. Interesting, the conformation among some clones whose CDR3 region contain different amino acid motif and did not use the same Jβ segment were high resemble. In conclusions, our findings described that the high frequency of TCR Vβ21 subfamily expansion emerged in p210BCR-ABL positive CML and B-ALL patients, and according to perplexing features of CDR3 region, it could not easy to confirmed that the oligoclonal expanded TCR Vβ21 subfamily must recognize to p210BCR-ABL protein, however, primary structure characterization of CDR3 region, in combination with spatial structure features, ultimately might help to identify the tumor-associated antigen immune attack on tumor cell in p210BCR-ABL positive CML or B-ALL patients. Disclosures:Li:The study was supported by grants from National “863” project (No. 2006AA02Z114) and Key project of Natural Science Foundation of Guangdong province, China (No. 05103293, 9251063201000001).: Research Funding.