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The function of CD14 in LPS signaling has remained enigmatic. Examination of the responses of cells and mice with defective CD14 shows that this molecule seems to modulate specific LPS recognition by TLR4.
Some microbes can circumvent phagocytosis by interfering with membrane transport systems. Brucella do this by making cyclic glucan molecules that interfere with lipid raft–mediated vacuole maturation.
The MAP3K kinases are thought to mediate signaling 'downstream' of the Toll-like receptors. Analysis of the MAP3K ASK1 demonstrates additional complexity in Toll-like receptor signaling pathways involving reactive oxygen species.
Cross-priming of cytotoxic T cells requires the transfer of antigens to dendritic cells from other cells. Careful analysis indicates that the antigens are peptides in association with chaperone proteins.
Hypermutation of antibody-producing B cells occurs in germinal centers, but how autoimmunity from the generation of potentially self-reactive antibodies is avoided has remained puzzling. Characterization of a new mouse mutant, sanroque, indicates previously unknown tolerance mechanisms act at this stage.
HIV pathogenesis is thought of as a chronic infection involving slow degradation of immunity that ultimately leads to AIDS. This scenario, however, could reflect the decay of an immune system mortally wounded during acute HIV infection.
The function of prostaglandin E2 in allergy has long been ambiguous. Now a comprehensive assessment of prostaglandin E2 receptor–deficient mice demonstrates the main anti-inflammatory function of this prostaglandin in allergic lung disease.
A newly identified crystal structure for an autoimmune TCR bound to peptide-MHC shows a highly unusual docking mode. Is this an anomaly or a new twist on MHC restriction?
Chemokines not only act as chemotactic and chemokinetic molecules but also are inducers of integrin-dependent adhesion. Analysis of an immunological synapse now demonstrates an additional function for chemokines as costimulatory molecules.
Chemokines 'trigger' the integrin LFA-1 to different conformational and affinity states. Elegant experiments provide new insights into the involvement of different LFA-1 affinity states in rapid lymphocyte arrest under flow.
Inflammatory signals must be resolved to avoid excessive tissue damage. The D6 chemokine receptor acts in this process by 'mopping up' proinflammatory β-chemokines.
The MAP kinase p38 is normally regulated by the MAPKKK-MAPKK pathway in mammalian cells. However, analysis of T cell signaling shows an alternative pathway for p38 activation exists.
Double-positive thymocytes are selected into the CD4 or CD8 lineage on the basis of their T cell receptor specificity. The transcription factor cKrox has been identified as being both required and sufficient to direct thymocytes undergoing positive selection to the CD4 lineage.
