Complementarity Determining Region 3 Repertoire of Clonal T Cell Receptor α Chain in Patients with Micrometastasis from Breast Cancer
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Graphical Abstract
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Abstract
Objective To analyze the clonality of the T cells and specific repertoire skewing of T cell receptor α (TCRα) chain in patients with micrometastasis from breast cancer, and to understand the molecular characteristics of anti-tumor T cell clones. Methods RT-PCR amplification of 32 subfamilies of the TCR AV CDR3 gene and immune spectratyping analysis were used to investigate the repertoire drift of TCR AV CDR3 and clonality of T cells in 10 patients with micrometastasis from breast cancer. The complete DNA sequence (CDS) of TCR AV subfamilies of monoclonal expansion were amplified by PCR. We constructed recombinant plasmid and sequenced. The sequences of TCRα chain and CDR3 were analyzed. Results TCR AV presented specific repertoire skewing in micrometastasis from 10 cases, and only 1-4 TCR AV subfamilies T cells were identified, respectively. Clonal expanded T cells included monoclonal, oligoclonal, oligoclonal trend and multiclonal patterns. The monoclonal expanded T cells had different CDR3 amino acid sequences, but there were some common amino acid motifs of TCR CDR3: AM and DDKII in case 4 and case 8. Conclusion There are diverse expression of TCR AV gene in patients with micrometastasis from breast cancer. The TCRAV gene usage may be closely related to the diversity of breast tumor antigens and the differential immune responses in individual patients. However common amino acid motifs of CDR3 found in some patients may be helpful for T cell-directed therapy for breast cancer.
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