The retroelement Lx9 puts a brake on the immune response to virus infection.

The notion that mobile units of nucleic acid known as transposable elements can operate as genomic controlling elements was put forward over six decades ago. However, it was not until the advancement of genomic sequencing technologies that the abundance and repertoire of transposable elements were revealed, and they are now known to constitute up to two-thirds of mammalian genomes. The presence of DNA regulatory regions including promoters, enhancers and transcription-factor-binding sites within transposable elements has led to the hypothesis that transposable elements have been co-opted to regulate mammalian gene expression and cell phenotype.

Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity.

Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20.

Cytosolic Recognition of RNA Drives the Immune Response to Heterologous Erythrocytes.

The archetypal T cell-dependent antigen is sheep red blood cells (SRBCs), which have defined much of what we know about humoral immunity. Early studies using solubilized or sonicated SRBCs argued that the intact structure of SRBCs was important for optimal antibody responses. However, the reason for the requirement of intact SRBCs for the response to polyvalent protein antigen remained unknown.

Cytokine Expression by T Follicular Helper Cells.

T follicular helper (Tfh) cells are a specialized subset of CD4 T cells located within temporary structures known as germinal centers (GC) formed within B cell follicles of secondary lymphoid organs. In the GC, Tfh cells facilitate the production of high-affinity antibodies through secretion of effector cytokines, such as IL-21 and IL-4, and through cell-to-cell interactions. The flow cytometric-based method described here allows the detection of intracellular cytokines within the Tfh population of secondary lymphoid organs (e.

Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells.

Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8 and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region.

IL-21 and IL-4 Collaborate To Shape T-Dependent Antibody Responses.

The selection of affinity-matured Ab-producing B cells is supported by interactions with T follicular helper (Tfh) cells. In addition to cell surface-expressed molecules, cytokines produced by Tfh cells, such as IL-21 and IL-4, provide B cell helper signals. In this study, we analyze how the fitness of Th cells can influence Ab responses.