Sequence Diversity and Expression Profiles of T Cell Receptor Beta Chain Constant Genes TRBC1 and TRBC2 in Canine Lymphoid Tumour Cell Lines and Normal Lymphocytes

TL;DR

This study explores the sequence and expression patterns of T cell receptor genes in dogs, revealing insights into immune-targeting strategies and tumor origins.

Contribution

The study reports previously unreported TRBC1 transmembrane variation and germline TRBC expression in canine B-cell lines.

Findings

TRBC1 transmembrane region shows variation, but extracellular domains are fully conserved.

Canine PBMCs show balanced TRBC1 and TRBC2 expression, while cell lines show skewed profiles.

Germline TRBC mRNA is present in some B-cell lines, suggesting insights into tumor developmental origins.

Abstract

The subtle sequence diversity and mutually exclusive expression patterns of T cell receptor beta chain constant genes, TRBC1 and TRBC2, in mature human T cells, provide the basis for immune‐targeting strategies designed to eliminate clonally expanded malignant T cells while sparing a subset of normal T cells capable of maintaining immunocompetence. The evolutionarily conserved gene arrangement and regulation of TRBC loci in mammals make these genes attractive targets for translational immune‐targeting strategies in companion species, including dogs. However, available TRBC sequence data relevant to common dog breeds remains limited. In this study, we investigated the sequence diversity and mRNA expression profiles of canine TRBC1 and TRBC2 genes in peripheral blood mononuclear cell (PBMC) samples representing 14 different dog breeds, and in six established canine haematopoietic cell lines of both T‐cell and non‐T‐cell origin (i.e., B and NK cell lines). Our analysis uncovered a previously unreported variation in the TRBC1 sequence encoding the transmembrane region but found no sequence diversity in the extracellular domain of TRBC1 and TRBC2. A nearly equal mRNA expression of TRBC1 and TRBC2 was consistently observed in bulk samples of canine PBMCs across all breeds, in contrast to canine cell lines, which exhibited a more skewed expression profile. Unexpectedly, germline mRNA expression of TRBC was present in some (i.e., CLB70, GL1) but not other (i.e., CLBL1) canine cell lines of B cell origin. In conclusion, our findings indicate that the fully conserved amino acid sequence in the extracellular domain of canine TCR beta chain variants presents a challenge for the development of differential therapeutic antibodies. Additionally, the presence of germline TRBC transcripts in certain canine B‐cell neoplasms, but not others, may provide additional insights into the developmental stages from which these neoplasms originate.

Figures