News & Views in 2001

Although some cellular responses induced by TLRs are abolished in MyD88-deficient mice, TLR4, unlike TLR9, can still induce activation of NF-κB and MAPKs. The discovery of a cytoplasmic adapter protein for TLR4, called TIRAP, helps explain this phenomenon.

Type 1 diabetes is preventable in animal models and predictable in humans. The increase in our knowledge of basic immunology has allowed the initiation of large-scale clinical efforts to prevent diabetes.

Rheumatoid arthritis affects millions of individuals worldwide. Luckily, it is the autoimmune disease with the most promising clinical results.

Graves' disease and other autoimmune syndromes affecting the thyroid are the archetypes of organ-specific autoimmunity. Despite intensive research, the relative contribution of genetic and environmental factors to disease pathogenesis is not clear. Here, the latest developments in understanding the determinants of these diseases are discussed.

Identification of SH2D1A as the defective gene in X-linked lymphoproliferative syndrome highlighted the importance of SAP in the regulation of T cell activation. New data suggest an alternative explanation for how SAP controls signaling.

Certain types of regulatory T cells are preferentially induced at mucosal surfaces to maintain tolerance. However, the mechanisms involved in their induction are unclear. New evidence suggests DCs orchestrate this mucosal tolerogenic immune response.

The molecular events behind T cell quiescence are poorly understood. Evidence is now emerging that the transcription factor LKLF can potentially programme cells to a resting state in a c-Myc–dependent manner.

Unlike the BCR, the TCR cannot undergo affinity maturation. However, T cells respond with greater sensitivity to antigen during an immune response. New evidence suggests T cells undergo avidity maturation to enhance T cell responsiveness in the absence of changes in intrinsic affinity.

Immunological synapse formation is essential for T cell activation. A recent paper in Science reports that immunological and neurological synapses utilize a common molecule, agrin.

γδ T cells are the misunderstood siblings of the antigen receptor family. A recent paper in Nature that describes the crystal structure of a γδ TCR should initiate a clearer understanding of these enigmatic cells.

A current paradigm has ICOS participating in T_H2 costimulation. New data indicates ICOS regulates not only T_H2 cells, but also T_H1s.

BLyS and family are known to affect B cells in a positive fashion. Knock-outs of BLyS receptors indicate some new functions, including negative regulation by one BLyS receptor, TACI.

Expression of mIgM was thought to be essential for the differentiation of B cells expressing antibodies of other classes. New evidence suggests isotype class switching to IgA can occur in the absence of mIgM.

T cells, move over. B cells are now reported, in a recent paper in Nature, to have their own immunological synapses with APCs. Only this time the antigen is whole and B cells don't keep it to themselves.

Our current understanding of lymphocyte migration across the endothelium includes four steps: attachment, rolling, arrest and diapedesis. New evidence suggests the involvement of another step, chemorheotaxis.

Genetic ablation experiments have shown that Vav is critical for TCR signaling. Evidence is now emerging that the Vav family of signaling molecules play a critical role in antigen receptor signaling in B cells as well as in T cells.

Multiple error-prone DNA polymerase appear to contribute to immunoglobulin somatic hypermutation. Genetic and biochemical data now indicate that DNA polymerase η may be responsible for the generation of some of the strand-biased hotspot A mutations in the immunoglobulin loci.

The events that enable polarization of T cells and migration across the vasculature to the target are largely unknown. New evidence suggests that PKC-β(I) may be pivotal in controlling this process.

Adjuvants and inflammation inhibit TCR ligation-induced apoptosis of T cells. Bcl-3 may enhance the increased T cell survival by positive regulation of NF-κB transcription factors.

NK cell receptors either activate or inhibit the fratricidal tendencies of NK cells. Structural analysis of receptor-ligand complexes of both types of receptors reveals striking similarities in form, despite the diverse function.