Volume 18 Issue 4, April 2017

Antibodies to neutralizing epitopes on hemagglutinin exhibit reproducible dynamic immunodominance patterns over time. Early responses target largely the Cb site, followed by Sb dominance and a concomitant rise in the diversity of neutralizing-antibody specificities.

THEMIS, the enigmatic regulator of T cell selection in the thymus, controls selection by oxidizing and suppressing the activity of the tyrosine phosphatase SHP-1.

Throughout ontogeny, the γδ TCR repertoire in human blood becomes less diverse and more focused, yet is private in nature, and specific adult γδ T cell subsets undergo substantial clonal expansion after challenge with cytomegalovirus.

O’Shea and colleagues review recent advances in Jak–STAT biology, focusing on immune cell function, disease etiology and therapeutic intervention, as well as broader principles of gene regulation and signal-dependent transcription factors.

Microglia are by far the best-characterized macrophages in the CNS, but non-parenchymal populations, such as those found in the meninges, are being increasingly studied. Prinz et al. review the ontogeny and functions of both parenchymal macrophages and non-parenchymal macrophages the CNS.

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.

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.

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.

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.

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.