Genomic specificity of anti-mouse TCR mAbs determined by single-cell RNAseq

J Immunol. 2025 Sep 1;214(9):2202-2210. doi: 10.1093/jimmun/vkaf094.

Abstract

T cells play a pivotal role in the immune system, relying on their somatically rearranged T cell receptor (TCR) to recognize peptide-MHC complexes. A comprehensive and extensively used set of monoclonal antibodies (mAbs) against TCR variable regions was generated in the previous century. The separate identification of mAb-specific TCR-V proteins and TRV genes has resulted in multiple nomenclatures, making their relationships unclear. To formally re-establish this link and determine patterns of reactivity within TRV subfamilies, we sorted T cells from C57BL/6 mice positive for any one of a panel of 22 anti-V mAbs and determined their TRV genes by single-cell TCRseq. RNAseq data revealed consistently higher expression of repeated elements from the ERV1-family LTR RLTR6Mm (mapping to Gm20400) in cells utilizing TRBV segments encoded within a 66 kb genomic region between TRBV23 and TRBV30. Our findings provide a comprehensive resource for anti-mouse TCR mAb specificity and insight into V-gene usage biases and T cell function.

Keywords: T cell receptor; antibodies; repertoire; variable region.

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / genetics
  • Antibodies, Monoclonal* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell, alpha-beta* / genetics
  • Receptors, Antigen, T-Cell, alpha-beta* / immunology
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods
  • Single-Cell Gene Expression Analysis
  • T-Lymphocytes* / immunology

Substances

  • Antibodies, Monoclonal
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta