Dual TCR-Expressing T Cells in Cancer: How Single-Cell Technologies Enable New Investigation.
Elizabeth M MuhowskiLaura M RogersPublished in: ImmunoHorizons (2023)
TCR diversity measures are often used to understand the immune response in cancer. Traditional measures of diversity rely on bulk RNA sequencing (RNAseq) of the β-chain variable regions. However, the full αβ TCR repertoire is a combination of both the α- and β-chains, which are encoded by separate genes. In contrast with bulk RNAseq, single-cell RNAseq (scRNAseq) allows paired chain analyses, yielding a more accurate measure of the repertoire. Interestingly, ∼30% of mature peripheral T cells express multiple TCR alleles (e.g., two α-chains) and may exhibit dual Ag specificity. scRNAseq has become increasingly common, and data from both human and animal studies are publicly available. However, routine workflows discard secondary TCR alleles and focus on a single TCR clone per cell. This perspectives piece emphasizes why this may not be good practice and highlights unanswered questions in the field of T cell dual specificity.
Keyphrases
- single cell
- regulatory t cells
- rna seq
- immune response
- papillary thyroid
- endothelial cells
- dendritic cells
- healthcare
- magnetic resonance imaging
- stem cells
- primary care
- high resolution
- gene expression
- clinical practice
- dna methylation
- squamous cell carcinoma
- inflammatory response
- genome wide
- mass spectrometry
- quality improvement
- big data
- lymph node metastasis
- case control
- electronic health record
- bone marrow
- contrast enhanced
- wild type
- chemotherapy induced