T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies.
T cell receptor convergence is an indicator of antigen-specific T cell response in cancer immunotherapies.
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作者：
Pan M;Li B
T 细胞能够有效消除病原体，并在适应性免疫反应中发挥至关重要的作用。 T 细胞受体 (TCR) 趋同是指 T 细胞共享具有相同氨基酸序列的相同 TCR，但由于密码子简并性而具有不同的 DNA 序列。我们使用从小鼠和人类样本中获得的单细胞免疫分析和批量 TCRβ 序列 (TCR-seq) 数据对 TCR 收敛进行了系统研究，发现了抗原特异性和收敛之间的密切联系。这种关联比 T 细胞扩增更强，T 细胞扩增是抗原特异性 T 细胞的假定指标。通过使用流式分选的四聚体+单T细胞数据，我们发现会聚T细胞在肿瘤微环境中富集新抗原特异性CD8+效应表型。此外，TCR 收敛表现出比现有 TCR 库指数更好的免疫治疗反应预测准确性。总之，会聚 T 细胞可能具有抗原特异性，并且可能是抗癌免疫治疗的新型预后生物标志物。
T cells are potent at eliminating pathogens and playing a crucial role in the adaptive immune response. T cell receptor (TCR) convergence describes T cells that share identical TCRs with the same amino acid sequences but have different DNA sequences due to codon degeneracy. We conducted a systematic investigation of TCR convergence using single-cell immune profiling and bulk TCRβ-sequence (TCR-seq) data obtained from both mouse and human samples and uncovered a strong link between antigen-specificity and convergence. This association was stronger than T cell expansion, a putative indicator of antigen-specific T cells. By using flow-sorted tetramer+ single T cell data, we discovered that convergent T cells were enriched for a neoantigen-specific CD8+ effector phenotype in the tumor microenvironment. Moreover, TCR convergence demonstrated better prediction accuracy for immunotherapy response than the existing TCR repertoire indexes. In conclusion, convergent T cells are likely to be antigen-specific and might be a novel prognostic biomarker for anti-cancer immunotherapy.