title: A Highly Focused Antigen Receptor Repertoire Characterizes γδ T Cells That are Poised to Make IL-17 Rapidly in Naive Animals.
abstract: Interleukin (IL)-17 plays a key role in immunity. In acute infections, a rapid IL-17 response must be induced without prior antigen exposure, and γδ T cells are the major initial IL-17 producers. In fact, some γδ T cells make IL-17 within hours after an immune challenge. These cells appear to acquire the ability to respond to IL-1 and IL-23 and to make IL-17 naturally in naïve animals. They are known as the natural Tγδ17 (nTγδ17) cells. The rapidity of the nTγδ17 response, and the apparent lack of explicit T cell receptor (TCR) engagement for its induction have led to the view that this is a cytokine (IL-1, IL-23)-mediated response. However, pharmacological inhibition or genetic defects in TCR signaling drastically reduce the nTγδ17 response and/or their presence. To better understand antigen recognition in this rapid IL-17 response, we analyzed the antigen receptor repertoire of IL-1R(+)/IL-23R(+) γδ T cells, a proxy for nTγδ17 cells in naïve animals directly ex vivo, using a barcode-enabled high throughput single-cell TCR sequence analysis. We found that regardless of their anatomical origin, these cells have a highly focused TCR repertoire. In particular, the TCR sequences have limited V gene combinations, little or no junctional diversity and much reduced or no N region diversity. In contrast, IL-23R(-) cells at mucosal sites similar to most of the splenic γδ T cells and small intestine epithelial γδ lymphocytes expressed diverse TCRs. This remarkable commonality and restricted repertoire of IL-1R(+)/IL-23R(+) γδ T cells underscores the importance of antigen recognition in their establishment/function.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors: Yu-Ling
authors: YL
authors: Wei
authors: Department of Medicine, Division of Gastroenterology, Stanford University School of Medicine , Stanford, CA , USA.
authors: Arnold
authors: A
authors: Han
authors: Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors: Jacob
authors: J
authors: Glanville
authors: Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors: Fengqin
authors: F
authors: Fang
authors: Merck Research Laboratories , Palo Alto, CA , USA.
authors: Luis Alejandro
authors: LA
authors: Zuniga
authors: Merck Research Laboratories , Palo Alto, CA , USA.
authors: Jacob S
authors: JS
authors: Lee
authors: Merck Research Laboratories , Palo Alto, CA , USA.
authors: Daniel J
authors: DJ
authors: Cua
authors: Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, CA , USA ; Program in Immunology, Stanford University School of Medicine , Stanford, CA , USA.
authors: Yueh-Hsiu
authors: YH
authors: Chien
keywords: IL-17+ γδ T cells; IL-1R+ γδ T cells; IL-23R+ γδ T cells; TCR repertoire; high throughput TCR sequencing; γδ T cells