Abstract
Objective: To study the characteristics of the T cell receptor (TCR) repertoire in cancer tissue, peripheral blood and regional lymph nodes (LNs) from patients with papillary thyroid carcinoma (PTC).Methods: PTC tissue, peripheral blood mononuclear cells (PBMCs) and regional LNs of six patients with papillary thyroid carcinoma were harvested. T cell receptor beta-chain (TCRβ) profiling was performed though high-throughput sequencing (HTS), and IMonitor, MiXCR and VDJtools were used to analyze the characteristics of the TCR repertoire.Results: The results of IMonitor and those of MiXCR and VDJtools were very similar. The unique CDR3 of TCRβ from LNs was higher than that of PBMCs, and the CDR3 of TCRβ from LNs was higher than that of PTC tissue. Shannon's diversity index, D50, inverse Simpson index_mean and normalized Shannon's diversity index_mean of CDR3 from LNs were higher than those of PTCs and PBMCs. The HEC (high expansion clones) rate of CDR3 sequences at the amino acid level in PTC tissue was higher than that of PBMCs, which was higher than that of LNs. The V-J HEC rate of CDR3 was highest in PTC tissue, followed by PBMCs and LNs.Conclusion: TCR CDR3 profiling showed differences among and within the PBMCs, PTC tissues and regional LNs of PTC, including unique CDR3, CDR3 HEC at the amino acid level, CDR3 V-J HEC at the amino acid level, Shannon's diversity index and D50. The TCRβ repertoire of PTC tissue, peripheral blood and regional LNs of PTC provide a reference for further study of immunity mechanisms against PTC.
Highlights
As an important part of the adaptive immune system, T cells can recognize potential pathogen-derived or abnormal peptides or epitopes
The average raw reads of peripheral blood mononuclear cells (PBMC), regional lymph node (LN), and papillary thyroid carcinoma (PTC) tissues by IMonitor were 8,885,766, 9,024,276, and 8,927,650, respectively, and there was no significant difference among the three groups, indicating that the sequencing depth was consistent
The average reads of PBMCs, LNs, and PTC tissues by MiXCR and VDJtools were 8,116,006, 8,273,136, and 6,520,701, respectively, and there was no significant difference among the three groups
Summary
As an important part of the adaptive immune system, T cells can recognize potential pathogen-derived or abnormal peptides or epitopes. TCRs are heterodimers composed of an α chain and a β chain (encoded by the TRA and TRB genes, respectively) or a γ chain and a δ chain (encoded by the TRG and TRD genes, respectively). The former is the most common, accounting for ∼95% of TCRs. During T cell maturation, there is random recombination of gene segments within the variable (V), diversity (D) and joining (J) regions of the TCR gene (VDJ recombination) to generate a large number of TCRs, which can identify many specific antigens. The TCR repertoire is difficult to study and analyze
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