Genomic Specificity of Anti-TCR mAbs determined by single-cell RNAseq

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 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 66kb genomic region between TRBV23 and TRBV30. Our findings provide a comprehensive resource for anti-TCR mAb specificity and insight into V-gene usage biases and T cell function.