●Proteasomes and their kin: proteases in the machine age. Pickart, C. M. & Cohen, R. E. Nature Reviews Molecular Cell Biology March (2004) This review article describes how 'chambered proteases', such as the 26S proteasome that is involved in the generation of peptides for antigen presentation, select the correct target proteins and processively degrade these molecules.

●Having it both ways: MHC recognition in cis and trans. Leibson, P. J. & Pease, L. R. Nature Immunology March (2004) One way by which natural killer (NK) cells recognize target cells involves the absence of a target-cell MHC class I ligand for inhibitory NK-cell receptors. However, a new study indicates that such NK-cell receptors can also bind MHC class I molecules on the NK cell and that such an interaction does not deliver an inhibitory signal. The balance between cis and trans interactions might determine the sensitivity of the NK cell for generating a cytotoxic response.

●Interplay between mycobacteria and host signalling pathways. Koul, A., Herget, T., Klebl, B. & Ullrich, A. Nature Reviews Microbiology March (2004)

●Behind the scenes of anergy: a tale of three E3s. Davis, M. & Ben-Neriah, Y. Nature Immunology March (2004) This News & Views article describes how ubiquitylation and non-proteasomal degradation of key signalling molecules (such as PLC-γ1, PKC-θ and RASGAP) by the E3 ubiquitin ligases Itch, Cbl-b and GRAIL is necessary for the induction of T-cell anergy. The authors suggest that this might result in rapid disintegration of the immunological synapse formed between a T cell and antigen-presenting cell.

●Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4+ lymphocytes. Matthews, T., Salgo, M., Greenberg, M., Chung, J., DeMasi, R. & Bolognesi, D. Nature Reviews Drug Discovery March (2004)

●Flu strikes the hygiene hypothesis. Umetsu, D. T. Nature Medicine March (2004) In contradiction to the hygiene hypothesis, recent research in mice has indicated that influenza virus can enhance, rather than inhibit, the development of asthma. However, this does not rule out a role for infection with other pathogens in reducing asthma susceptibility.

●HIV escape: there and back again. Altman, J. D. & Feinberg, M. B. Nature Medicine March (2004) A News & Views article describing how selection pressures to escape detection by cytotoxic T lymphocytes are balanced by effects on viral fitness in determining which of the genetic variants of HIV-1 that emerge in infected individuals can persist and be transmitted to new hosts. Such information is crucial for the design of an effective vaccine.