Opinion in 2008

This article proposes that endogenous peptides can enhance the recognition of antigenic peptides by T cells and, based on results from MHC class I- and class II-restricted T-cell systems, that CD4 and CD8 have different roles in the recognition of endogenous peptide–MHC complexes.

These authors express their opinion that we should devote more research attention to uncovering the mechanisms by which a host can tolerate, as well as resist, infection with a pathogen. New drugs to increase tolerance to infection should provide therapies to which pathogens will not develop resistance.

The activation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors influences signalling pathways downstream of other receptor types. In this Opinion, Lionel Ivashkiv describes how ITAM-dependent signalling can differentially influence cellular responses to Toll-like-receptor ligands and cytokines.

In this Opinion article, Stephen Galli and colleagues discuss the recent evidence that mast cells can have negative, as well as positive, immunomodulatory functions, and suggest that mast cells might have distinct roles at different phases of an immune response.

Accumulating evidence suggests that B cells can regulate immune responses. Here, the authors present a model to explain how B cells may regulate autoimmune pathology by secreting interleukin-10 in response to Toll-like receptor triggering and thereby mediate immune suppression.

Given that T-cell receptor (TCR) repertoires are randomly generated, how come T cells bearing identical TCRs often dominate the response to an antigen in many individuals? Here, the authors provide a molecular explanation to the conundrum of public T-cell responses.

Several models have been proposed to explain how cytotoxic T-lymphocyte antigen 4 (CLTA4) regulates T-cell activation but no model fully accounts for its overall function. Here, Christopher Rudd presents a new reverse stop-signal model, which can potentially explain multiple aspects of CTLA4 function.

Distinct members of the interleukin-12 (IL-12) cytokine family can differentially regulate T-cell-mediated inflammation. In this Opinion article, the authors propose that microbial products and endogenous mediators can control the balance between these cytokines, thereby directly regulating the inflammatory response.

How do antigenic tumour cells and chronic pathogens exploit natural regulatory mechanisms to become non-immunogenic? Andrew Mellor and David Munn propose that such immune unresponsiveness is an indirect consequence of the need to control the potentially lethal consequences of unrestrained immunity to innocuous substances.