Volume 13 Issue 3, March 2012

It is unknown how T cell antigen receptors from autoreactive CD8⁺ T cells recognize self. A new paper shows that an unorthodox, low-affinity way of interacting with targets may be at the basis of autoimmunity.

The invariant chain CD74 prevents the loading of peptides derived from endogenously synthesized proteins onto major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum. CD74 is now shown to serve a similar function for some MHC class I molecules.

Dynamic imaging portrays intraepidermal T cells as truly autoreactive, constitutively transmitting signals from a putative ligand expressed by normal epithelial cells.

Maturation of the proinflammatory cytokine IL-1b is achieved mainly by the canonical caspase-1 inflammasome. An alternative caspase-8-dependent inflammasome that is engaged after stimulation with dectin-1 during fungal and mycobacterial infection has now been described.

SAMHD1 restricts the infection of dendritic cells by human immunodeficiency virus type 1. Margottin-Goguet and colleagues show that SAMHD1 limits viral DNA synthesis by hydrolyzing intracellular dNTPs.

Nuocytes are innate cells with critical roles during infection with parasitic worms. McKenzie and colleagues show that nuocytes differentiate from common lymphoid progenitors and require IL-7, IL-33, Notch and RORα for development.

The invariant chain CD74 is involved in the formation of major histocompatibility complex class II. Jefferies and colleagues show that it also associates with class I in the endolysomal compartment and is important in cross-presentation.

Production of the proinflammatory cytokine IL-1β is crucial in host defense. Geijtenbeek and colleagues show that dectin-1 signaling in response to fungi and mycobacteria induces IL-1β maturation via a noncanonical caspase-8-dependent inflammasome.

Autophagosomes deliver cytoplasmic constituents to lysosomes for degradation. Kehrl and colleagues show that inflammasome activation triggers autophagosome formation, which in turn eliminates active inflammasomes.

The mechanisms by which TCR signaling 'instructs' thymic lineages remain unclear. Bendelac and colleagues show that the TCR-induced transcription factor Egr2 specifies the early and late stages of differentiation into the natural killer T cell lineage.

The γδ dendritic epidermal T cells (DETCs) can recognize stress-affected cells. Zal and colleagues show that at steady state, V_γ5 TCRs form immunological synapses that anchor DETC projections to the tight junctions of squamous keratinocytes.

Much is known about crystal structures of MHC class II–autoreactive TCRs. Sewell and colleagues provide the structure of an MHC class I–autoreactive TCR and provide insight into the molecular basis of its diabetogenicity.

IL-35 is an immunomodulatory cytokine, but the molecular details of its effects have remained obscure. Vignali and colleagues determine the IL-35 receptor and how its signaling pathway leads to its suppressive action.

Cycling and cell cycle–arrested pre-B cells both express pre-BCRs, but whether qualitative differences exist in downstream signaling pathways remains controversial. Singh and colleagues show that differences in expression of the adaptor BLNK underlie functional distinctions in pre-BCR signaling.