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The molecular mechanisms behind recognition of altered self remain unclear. Moore and co-workers show that oxidized low-density lipoprotein (LDL) and β-amyloid trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6.
CTLA-4-deficient mice develop a lethal multiorgan lymphoproliferative disorder. Murphy and colleagues definitively demonstrate that at least some of the pathogenic T cells that drive this disorder show reactivity to nonlymphoid tissue self antigens.
The signaling intermediates that activate inflammasomes have remained elusive. Tschopp and co-workers now describe that a thioredoxin-binding protein is a reactive oxygen species–regulated component of the NLRP3 inflammasome.
Natural killer cells infiltrate the pancreas during type 1 diabetes. Mandelboim and co-workers find that the natural killer receptor NKp46 recognizes ligands on pancreatic beta cells and is essential for full diabetes development.
Pre-TCR signaling is essential for the passage of thymocytes through the β-selection checkpoint. Ravichandran and co-workers find that CXCR4 acts as a costimulator for the pre-TCR and is needed for optimal progression through β-selection.
TCR movement in the T cell plasma membrane is not well understood. Using three different types of microscopy, Davis and co-workers identify separate islands of Lat and TCR molecules that concatenate after T cell activation.
Immunoglobulin diversification is absolutely dependent on the action of activation-induced cytidine deaminase, which must be tightly controlled. Honjo and colleagues systematically analyze the regulatory elements that govern expression of the gene encoding this deaminase.
Data management has been neglected but should be made an integral activity in all research laboratories. Chaussabel and colleagues discuss how to implement this at the bench.
Nucleotide-binding oligomerization domain 2 (Nod2) is required for sensing of intracellular bacteria and subsequent inflammatory responses. Unexpectedly, new evidence suggests that Nod2 influences T helper cell signaling, proliferation and differentiation and effector responses against Toxoplasma gondii.
The differentiation of interleukin 17–producing helper T cells is controlled by a complex network of cytokines, signaling pathways and transcription factors. Regulation by microRNA particles can now be added to this list.
Antigen-driven selection in germinal centers lays the foundation of effective B cell memory. Two reports in this issue reveal novel mechanisms that control effective formation of germinal centers and their long-term persistence in vivo.