Recent findings indicate the presence of T cell receptor(TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages.In this study,using a semiquantitative trilineage immune reper...Recent findings indicate the presence of T cell receptor(TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages.In this study,using a semiquantitative trilineage immune repertoire sequencing approach as well as under rigorous bioinformatic conditions,we identify highly complex TCRβtranscriptomes in human circulating monocytes and neutrophils that separately encode repertoire diversities one and two orders of magnitude smaller than that of T cells.Intraindividual transcriptomic analyses reveal that neutrophils,monocytes,and T cells express distinct TCRβrepertoires with less than 0.1%overall trilineage repertoire sharing.Interindividual comparison shows that in all three leukocyte lineages,the vast majority of the expressed TCRβvariants are private.We also find that differentiation of monocytes into macrophages induces dramatic individual-specific repertoire shifts,revealing a surprising degree of immune repertoire plasticity in the monocyte lineage.These results uncover the remarkable complexity of the two phagocyte-based flexible immune systems which until now has been hidden in the shadow of T cells.展开更多
基金supported by a grant from the Stiftung für Pathobiochemie und Molekulare Diagnostik of the Deutsche Vereinte Gesellschaft für Klinische Chemie und Labormedizin(DGKL),Germany(Grant No.FUCHS 5-2015)。
文摘Recent findings indicate the presence of T cell receptor(TCR)-based combinatorial immune receptors beyond T cells in neutrophils and monocytes/macrophages.In this study,using a semiquantitative trilineage immune repertoire sequencing approach as well as under rigorous bioinformatic conditions,we identify highly complex TCRβtranscriptomes in human circulating monocytes and neutrophils that separately encode repertoire diversities one and two orders of magnitude smaller than that of T cells.Intraindividual transcriptomic analyses reveal that neutrophils,monocytes,and T cells express distinct TCRβrepertoires with less than 0.1%overall trilineage repertoire sharing.Interindividual comparison shows that in all three leukocyte lineages,the vast majority of the expressed TCRβvariants are private.We also find that differentiation of monocytes into macrophages induces dramatic individual-specific repertoire shifts,revealing a surprising degree of immune repertoire plasticity in the monocyte lineage.These results uncover the remarkable complexity of the two phagocyte-based flexible immune systems which until now has been hidden in the shadow of T cells.