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Love and colleagues show that THEMIS enhances the TCR signaling response to low-affinity ligands by inhibiting the tyrosine-phosphatase activity of SHP-1.
B-1a B cells are a distinct subset of mature B cells that provide innate-like protection against pathogens. Busslinger and colleagues identify the transcription factor Bhlhe41 as being essential for B-1a development and self-renewal.
γδ T cells are generally understood to be innate lymphocytes. Prinz and colleagues show that human γδ T cells reconstituted after bone-marrow transplantation have a distinct repertoire that can be shaped by infection with cytomegalovirus, which suggests features of adaptive immunity.
CD8+ T cells rapidly commence transcriptional changes after antigenic encounter and priming. Yeo and colleagues find substantial transcriptional heterogeneity among responding lymphocytes, particularly at the first division, that influences cell fate.
Silencing of the chromatin remodeler Mi-2β in keratinocytes triggers local skin inflammation. Regulatory T cells activated by the cytokine TSLP control the shift from local skin inflammation to systemic lethal disease.
Elevated signaling via the metabolic checkpoint kinase mTORC1 in macrophages stimulates spontaneous granuloma formation in mice and is associated with the progression of sarcoidosis in humans.
Interleukin 1β (IL-1β) is a cytokine associated with inflammation, obesity and metabolic dysregulation. Surprisingly, IL-1β is also required for maintaining steady-state glucose homeostasis by potentiating postprandial insulin secretion.
Rosenberg and colleagues review evidence suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans.
Antigenic epitopes differ in their immunogenicity. Yewdell and colleagues show that B cell and antibody responses to influenza A virus infection display reproducible dynamic immunodominance hierarchies to viral hemagglutinin epitopes.
Antigenic drift and reassortment alters the epitopes of influenza virus. Krammer and colleagues reveal the cross-reactivity of antibody responses to viral hemagglutinin and neuraminidase in humans and several animal models, but the most prominent responses reflect ‘original antigenic sin’ to viral exposure.
Mucosal-associated invariant T cells recognize vitamin-B-derived ligands presented via the major-histocompatibility-complex-like molecule MR1. Rossjohn and colleagues demonstrate that these cells recognize a wide variety of ligands, some derived from common drugs, in an agonist or antagonist manner.
Tr1 cells have potent regulatory effects in vitro and in vivo. Kuchroo and colleagues comprehensively describe the epigenetic, transcriptional and gene regulatory landscape that is essential for Tr1 cell differentiation.
Natural killer T cells (NKT cells) are thought to originate at the double-positive stage of thymopoiesis. Taniguchi and colleagues find that a subset of NKT cells also appear earlier, at the double-negative stage, and that these give rise to liver-resident NKT cells with highly potent effector function.