scRNA+TCR-seq Reveals the Proportion and Characteristics of Dual TCR Treg Cells in Mouse Lymphoid and Non-lymphoid Tissues

Abstract

The rearrangement of TCR germline V(D)J genes during T cell development, including allelic exclusion and tolerance selection, ensures the clonal selection theory, which states that "a lymphocyte expresses only one type of antigen receptor" This forms the basis for T cell-specific responses. However, The existence of "dual TCR T cells" has consistently been supported by specific experimental evidence. detailed reports on the origin, proportion, tissue distribution, and CDR3 characteristics of "dual TCR Treg cells" are currently lacking. In this study, we utilized scRNA+TCR-seq technology to achieve in-depth analysis of single TCR T and dual TCR T pairings, along with their mRNA expressions, from over 5,000 T cells in each sample. Through comparative studies with shared databases, we provided a detailed analysis of the proportions and characteristics of dual TCR Tregs in mouse lymphoid and non-lymphoid tissues (such as iLN, mLN, blood, and skin). Our findings revealed a high proportion of dual TCR Tregs across various mouse tissues, with their TCR pairing patterns, V(D)J usage, and mRNA expression showing both homogeneity and certain differences compared to single TCR Tregs, as well as heterogeneity across different tissue sites. This research provides new insights and technical approaches for studying the origins, characteristics, effects, and mechanisms of Treg cells in different tissue locations.