Reviews & Analysis

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.

Differentiation of periperal T cells into T_H1 and T_H2 subsets is a crucial part of a normal immune response. Evidence is emerging that a signaling pathway involving the SAP molecule may play an important role in this differentiation process.

Activation, proliferation and differentiation of CD8⁺ cytotoxic T cells must be carefully regulated. New evidence suggests that antigen and costimulation may be enough to trigger the program.

The disappearance of CD4⁺ T cells during an HIV infection sets the stage for the characteristic immunodeficiency. But how do the virally infected cells protect themselves long enough to manufacture more HIV virions? A recent paper in Nature suggests that Nef may be part of the answer.

Proteins are digested into peptides for presentation by MHC to T cells. A recent paper in Science reports that some lipids also undergo processing in order to be presented by the unconventional class I protein CD1.

New data shows that NADPH oxidase activation by Rac2 involves an insert-dependent interaction between Rac2 and cyt b. This unique activation mechanism has far-reaching implications for the regulation of related signaling systems.

In addition to the TCR and classical MHC class I, MHC class 1–like molecules can interact with a variety of receptors that play a role in T cell activation. Engagement of NKG2D on CMV-specific αβ CD8⁺ cells by MIC was found to provide them with a costimulatory signal and augment their cytotoxic response.

Notch is heavily involved in T cell lineage commitment . . . or is it? New data indicates that neither CD4 nor CD8 cell maturation is Notch1-dependent, whereas Notch1 is critical for earlier steps in T cell development.

What determines whether immune responses against a self-peptide can evoke an anaphylactic response? New evidence describes anaphylaxis that appears to be governed by thymic expression of the self-antigen.

A minimal half-life of the TCR-pMHC interaction is required for complete T cell signaling (the kinetic proof reading model). In an extension to this model it is clear that the dwell time or half-life of TCR-pMHC interaction is also critical for T cell activation

Secretion of IFN-γ by T cells is usually the result of antigen stimulation. However, a newly identified GADD45β pathway can implement IFN-γ production after exposure to cytokines IL-18 and IL-12 without need of antigen.

Three recent papers in Nature describe ICOS-deficient mice. ICOS is necessary for normal antibody responses and may be protective against autoimmunity.