Nature Immunology pp 127 - 134

T cells normally bear only one type of T cell receptor (TCR) for antigen on the cell surface but a few can bear two. Having more than one is thought to be detrimental, because the second may cause autoimmune diseases. In the February issue of Nature Immunology, scientists show that these so-called dual TCR cells actually play a beneficial role in the immune system by increasing the ability of T cells to recognize invading microbes.

Charles Janeway and colleagues from Yale University School of Medicine have found that each TCR on dual TCR cells plays a different role. In their mouse model, one of the TCRs allows the T cell to develop and enter the blood stream, whereas the other, nonselected, TCR recognizes foreign matter that the first TCR is not capable of seeing. Thus, dual TCR cells can benefit the immune response by increasing the likelihood that T cells will recognize and eliminate foreign matter from the body. This would explain why dual TCR cells are retained at low frequencies in healthy individuals—the benefit of having such cells around apparently outweighs the potential risk of inducing autoimmune disease.

Nature Immunology pp 169 - 174 and pp 175 -181

Autoimmunity results when a patient's immune system recognizes self molecules as foreign and turns on its own tissues. How this recognition process occurs, and is avoided by healthy individuals, is subject to intense research efforts. Two papers in the February issue of Nature Immunology explain how bits of protein recognized by pathogenic immune cells can be hidden from immune cells by the action of a protein scissors, known as an endopeptidase.

Using an experimental model of multiple sclerosis, Anderton and colleagues at the University of Edinburgh identified the precise bits of myelin basic protein (MBP), a protein implicated as the disease target, that are recognized by pathogenic T cells. Only one particular region of the protein elicited pathogenic responses; however, this region is usually hidden from immune surveillance. Researchers headed by Colin Watts at the University of Dundee found why this dominant protein recognition element is often absent. Protein cleavage by an enzyme called asparaginyl endopeptidase destroys this region of MBP, preventing antigen-presenting cells from showing this protein bit to T cells. Thus, differences in the expression of this processing enzyme might explain why some tissues are targeted by potentially self-reactive immune cells.

Nature Immunology pp 182 - 188

Antibodies (also known as immunoglobulins) circulate throughout the body and help neutralize pathogens. In a paper published in the February issue of Nature Immunology investigators from Australia show why one type of B cell tends to win out over another in the bodys attempt to fill the bloodstream with the most efficient and effective antibodies. It turns out that the particular "brand" of antibody that the B cells make actually governs the fitness of the B cell for survival.

In an initial infection, B cells produce antibodies called IgM, which are usually of low affinity, and therefore bind to a number of targets, but they do not bind very well. During infections, toxins may be present that need immediate neutralization, and IgM helps by getting rid of some of it. However, IgG antibodies, which have higher affinities and more precise specificities, are much more effective weapons and predominate in memory responses (such as those after an immunization or after re-exposure to the same microbe). Christopher Goodnow and colleagues from Canberra, Australia genetically manipulated these two kinds of antibodies so that they only differed in their tails that protrude into the cytoplasm of the B cells. The other end of the antibody binds to the antigen—all antibodies in the experimental setup had the same antigen-binding site. They found that the IgG tail, but not that from IgM, enables B cells to survive longer, allowing them ultimately to produce a greater amount of antibodies. This explains why in a memory response much more specific IgG is produced and the response is much more effective.

Nature Immunology pp 189 - 195

The number of killer CD8 T cells in the body contracts following the eradication of virus-infected cells but this decline in numbers does not equate with the drop in measurable killer activity, which is much quicker. In Nature Immunology, scientists have shown that during viral infection, an inhibitory receptor, CD94-NKG2A, is expressed by the killer T cells and is responsible for shutting down the cells killing machinery.

Aron Lukacher and colleagues from Emory University School of Medicine and the National Institutes of Health used a mouse model to analyze the role of CD94-NKG2A on killer T cells during polyoma virus infection. This virus persists for life in mice but is normally controlled by the killer T cells. In a few susceptible mice, despite the presence of killer cells this virus can cause cancer. Lukacher and colleagues have shown that CD94-NKG2A expressed on the surface of CD8 T cells prevents these cells from killing the virus, which is therefore free to cause cancer. Clearly, precise control of CD94-NKG2A expression during an immune response is critical because an imbalance can lead to the dysfunction of killer T cells.