T-cell responses

IFN-γ represses IL-4 expresssion via IRF-1 and IRF-2. Elser, B. et al. Immunity 17, 703–712 (2002)

On the basis of patterns of cytokine expression, CD4+ T cells can be divided into TH1 and TH2 cells. IFN-γ assists TH1-cell development, but until now, a direct effect of IFN-γ on the expression of TH2 cytokines has not been shown. This study shows that IFN-γ represses the expression of IL-4, a crucial TH2-inducing cytokine, by inducing the expression of interferon regulatory factor 1 (IRF1) and IRF2, which bind to sites in the IL-4 promoter and suppress its activity.

Natural killer cells

A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition. Michaëlsson, J. et al. J. Exp. Med. 196, 1403–1414 (2002)

Interaction of HLA-E — a non-classical MHC molecule that presents mainly peptides derived from other MHC class I molecules — with the inhibitory NK-cell receptor CD94–NKG2A prevents the activation of NK cells. This study shows that HLA-E can present a peptide from HSP60 (the expression of which is upregulated in stressed cells), which prevents the complex from being recognized by CD94–NKG2A. A greater number of such complexes are likely to be expressed by stressed cells, which could block inhibitory signalling and allow NK cells to kill stressed cells.

Signalling

Non-T-cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signalling. Brdicka, T. et al. J. Exp. Med. 196, 1617–1626 (2002)

Linker for activation of T cells (LAT) is an important component of TCR signalling pathways. However, B cells and natural killer (NK) cells do not express LAT. Do they express a LAT-like molecule? Here, Brdicka et al. identify a new transmembrane adaptor protein that is structurally and evolutionarily related to LAT, known as non-T-cell activation linker (NTAL), which is expressed by B cells, NK cells, monocytes and mast cells, and which seems to function in a LAT-like manner.

Innate immunity

Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. Yamamoto, M. et al. J. Immunol. 169, 6668–6672 (2002)

Although the TIR-domain-containing adaptor TIRAP was thought to mediate signalling from TLRs through the MYD88-independent pathway, this was shown recently not to be the case. Now, Yamamoto et al. report the identification of a new adaptor, TIR-domain-containing adaptor inducing IFN-β (TRIF). Studies using a dominant-negative form of TRIF show that it is involved in TLR signalling, particularly in the MYD88-independent pathway.