Mapping the spatial distribution of T cells in repertoire dimension

• DOI: 10.1016/j.molimm.2021.08.009
• Publication Date: 2021-08-21T21:26:07Z
• Authors: Junying Zhang; Yu Wang; Haili Yu; Gang Chen; Liting Wang; Fang Liu; Jiangbei Yuan; Qingshan Ni; Xuefeng Xia; Ying Wan
• Keywords: Public clonotypes; 0303 health sciences; T-Lymphocytes; Receptors, Antigen, T-Cell; Tissue location; Similarity; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; TCR sequencing; Animals; Female; T cell receptor

T cells mediate adaptive immunity in diverse anatomic compartments through recognition of specific antigens via unique T cell receptor (TCR) structures. However, little is known about the spatial distribution of an organism's TCR repertoire. Here, using high-throughput TCR sequencing (TCRseq), we investigated the TCR repertoires of sixteen tissues in healthy C57B/L6 mice. We found that TCR repertoires generally classified into three categories (lymph nodes, non-lymph node tissues and small intestine) based on sequence similarity. Clonal distribution and diversity analyses showed that small intestine compartment had a more skewed repertoire as compared to lymph nodes and non-lymph node tissues. However, analysis of TRBV and TRBJ gene usage across tissue compartments, as well as comparison of CDR3 length distributions, showed no significant tissue-dependent differences. Interestingly, analysis of clonotype sharing between mice showed that although non-redundant public clonotypes were found more easily in lymph nodes, small intestinal CD4 + T cells harbored more abundant public clonotypes. These findings under healthy physiological conditions offer an important reference dataset, which may contribute to our ability to better manipulate T cell responses against infection and vaccination.