Reviews & Analysis

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.

In addition to conventional interactions between receptors and ligands on opposing cells (trans interactions), some MHC-class-I-specific receptors interact with their ligands on the same cell (cis interactions). Here, the structural characteristics and functional outcome of cisinteractions are discussed.

Understanding the mechanisms of allergic inflammation is important for the improvement of current therapies and the development of novel therapies. This Review describes the current therapeutic strategies for allergy and asthma and highlights several innovative future strategies.

Asthma and chronic obstructive pulmonary disease both involve chronic inflammation of the lungs. But Peter Barnes explains how the inflammatory mediators and cells involved differ between the two diseases and how this affects their responsiveness to corticosteroids and other anti-inflammatory therapies.

Here, John Harty and Vladimir Badovinac describe the factors that control the generation of memory CD8⁺ T cells, discuss how these factors can characterize this response and highlight how the manipulation of these factors could reshape CD8⁺T-cell memory.

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.

Views about the differentiation pathways of haematopoietic-cell lineages are evolving. No longer viewed as a series of binary fate decisions, evidence is emerging for the divergence, convergence and reversibility of haematopoiesis, as described here for B-cell development.

The immune system has evolved specific mechanisms to deal with the unique problems encountered in the specialized microenvironment of the lung. This Review discusses the key mechanisms through which the local immune system maintains immunological homeostasis in the lung while preserving the integrity of the gas-exchange surfaces.

Studies inDrosophila melanogasterare proving fruitful for our understanding of phagocytosis in development, tissue homeostasis and host defence. In this Review, parallels are drawn between phagocytosis in flies and mammals, providing insight into its complexity and the evolutionary origins of immunity.

In this article, the authors provide a description of microRNA production and function, and discuss what is currently known about the role of microRNAs in the development and function of immune cells and in host–virus interactions.

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.

The recent resolution of the long-awaited structures of the central components of the complement system — C3 and factor B — has finally revealed the molecular details of complement activation. With this, clues to how complement activation is regulated and evaded by pathogens are also emerging.

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.

The function of the various subclasses of IgG molecules is mediated by the family of Fc receptors for IgG (FcγRs). This Review outlines how FcγRs regulate immune responses and the relevance of this information to developing new therapies for treating human diseases.

Here, the authors describe how the antitumour effects of many conventional cancer treatments involve the immune system, by promoting immunogenic tumour-cell death or by direct stimulation of immune cells. Taking advantage of this 'bystander effect' may help in the fight against cancer.

In this article, Ellen Rothenberg and colleagues review the key transcription factors and other regulatory factors involved in the processes of specification and commitment to the T-cell lineage, and outline the outstanding questions in the field.

Germinal centres are the main source of memory B cells and plasma cells that produce high-affinity antibodies in the body. In this Review, Ulf Klein and Riccardo Dalla-Favera describe the relationship between the cellular and molecular dynamics of germinal centres and the pathogenesis of B-cell lymphomas.