Helium core

Stellarenvelope

Soundwaves

Buoyancywaves

T R A V I S S . M E T C A L F E

Just as in Hollywood, the age of a star is not always obvious if you look only at the sur-face. During certain phases in a star’s life,

its size and brightness are remarkably con-stant, even while profound transformations are taking place deep inside. For most of their existence, stars shine from the energy released by nuclear reactions that convert hydrogen into helium, but eventually they begin to burn the helium in their cores to synthesize heavier elements, such as carbon and oxy-gen. On page 608 of this issue, Bedding et al.1 demonstrate a new technique for distinguish-ing between these life stages, using continu-ous ‘starquakes’ to probe the deepest regions, where the changes are most dramatic.

The objects examined by Bedding and col-leagues are known as red giants, the bloated fate of stars such as our Sun as they begin to exhaust their primary source of energy — the hydrogen near the centre that powers nuclear fusion. The resulting helium accumulates in the core, forcing hydrogen in a surrounding shell to burn more vigorously than before. About 5 billion years from now, these processes will gradually cause our own star to expand to more than 100 times its present size, becoming a red giant and destroying some of the inner planets in the Solar System2. Stars that were born before the Sun, as well as heavier stars (which evolve more quickly), have already reached this phase of stellar evolution.

Like the Sun, the surface of a red giant seems to boil as convection brings heat up from the interior and radiates it into the coldness of outer space. These turbulent motions act like continuous starquakes, creating sound waves that travel down through the interior and back to the surface. Some of the sounds have just the right tone — a million times lower than the audible range for humans — to set up standing waves (known as solar-like oscil-lations) that cause the entire star to change its brightness regularly over hours and days, depending on its size. Inferring the properties of stars from these periodic brightness changes is a technique known as asteroseismology3.

The sound waves generated near the surface of a red giant can interact with buoyancy waves (rather like the waves in the ocean) that

are trapped inside the helium core. Under the right conditions, the two types of waves can couple to each other, changing the regularity of the brightness changes at the surface. These ‘mixed’ oscillation modes are much more sensitive to structure in the core than are the uncoupled sound waves that sample only the stellar envelope (Fig. 1).

The innovation that allowed Bedding et al.1 to distinguish between red giants at different life stages emerged from precise observations by the Kepler space telescope. Launched in March 2009, Kepler stares at a large patch of sky near the constellation Cygnus, monitor-ing the brightness of more than 156,000 stars with the goal of detecting Earth-like planets. The mission has been extremely successful at

finding alien worlds4, but it is also revolution-izing the study of stellar oscillations by pro-viding many months of continuous data for

thousands of stars5,6. Earlier efforts to study red giants from ground-based telescopes

were hampered by both the daily inter-ruptions of sunlight and the limited

duration of the monitoring.As mentioned before, the trouble

with red giants is that they all look nearly the same on the outside, regardless of their mass and age. Bedding and colleagues1 sought to determine these properties for the hundreds of red giants observed by the Kepler satellite, to measure

precisely when stars of a given mass would shift from burning hydrogen in

a shell to helium in the core. The regular pattern of standing waves is insufficient to

pinpoint which energy source makes a partic-ular red giant shine, but the mixed oscillation modes exhibit a unique pattern7. By decipher-ing this pattern, Bedding et al.1 demonstrate how the two life stages of red giants can be separated using asteroseismology.

The life story of a red giant theoretically depends not only on its age but also on its mass, with stars smaller than about twice the mass of the Sun experiencing a sudden igni-tion known as a helium flash. The temperature required to fuse helium is significantly higher than that needed for hydrogen, and in low-mass stars the helium accumulates in the core at very high density until it reaches a critical size and ignites almost instantaneously. In more massive stars, the transition to helium core burning is gradual, so the stars exhibit a wider range of core sizes and never experience a helium flash. Bedding and colleagues show how these two populations can be distinguished observationally using their oscillation modes, providing new data to validate a previously untested prediction of stellar evolution theory.

This extraordinary peek into the inner lives of red giants was made possible by just the first year of observations from the Kepler mission, which is scheduled to operate for at least 3.5 years and might be extended by NASA for a further 2.5 years. The picture that emerges from asteroseismology will stead-ily improve as the observations continue, so

A S T R O P H Y S I C S

The inner lives of red giantsThe natural pulse of a red-giant star provides crucial insight into what makes it shine. Observations of red giants by the Kepler space telescope shed light on a previously untested prediction of stellar evolution theory. See Letter p.608

Figure 1 | Red-giant oscillations. Turbulent motions inside a red-giant star act like continuous starquakes, creating sound waves that travel down through the interior and back to the surface. Under the right conditions, these standing waves can couple with buoyancy waves trapped inside the helium core. Bedding et al.1 identify these ‘mixed’ oscillation modes in hundreds of red giants observed by the Kepler space telescope, providing unique tests of stellar evolution theory.

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we can expect even better results for the stars examined by Bedding et al.1, as well as simi-lar measurements for other red giants, in the near future. ■

Travis S. Metcalfe is at the High Altitude Observatory, National Center for Atmospheric Research, Boulder, Colorado 80307-3000, USA. e-mail: travis@ucar.edu

1. Bedding, T. R. et al. Nature 471, 608–611 (2011).2. Silvotti, R. et al. Nature 449, 189–191 (2007).3. Aerts, C., Christensen-Dalsgaard, J., Cunha, M. &

Kurtz, D. W. Sol. Phys. 251, 3–20 (2008).4. Borucki, W. J. et al. Astrophys. J. 728, 117–137

(2011).5. Gilliland, R. et al. Publ. Astron. Soc. Pacif. 122,

131–143 (2010).6. Chaplin, W. J. et al. Science (in the press). 7. Beck, P. G. et al. Science doi:10.1126/

science.1201939 (2011).

I M M U N O L O G Y

Cross-dressers turn on T cells Memory T cells remember viruses from previous infections, providing immunity by facilitating the killing of infected cells. For this, they exploit cross-dressing, the transfer of antigens between antigen-presenting cells. See Letter p.629

J O N A T H A N W. Y E W D E L L & B R I A N P. D O L A N

As their name suggests, antigen-present-ing cells flag up the presence of foreign molecules (antigens) to killer T cells of

the immune system, triggering the appropriate immune response. The cells generally acquire antigens in one of two ways: by direct presenta-tion, in which the cell itself is infected with the antigen it presents; and by cross-presentation, in which the presenting cell engulfs compo-nents of an infected cell and then processes and presents the associated antigen. A third mechanism — cross-dressing — has also been postulated1–3, in which an antigen-presenting cell acquires the requisite processed anti-gen directly from another infected antigen- presenting cell. On page 629 of this issue, Wakim and Bevan4 report the strongest evi-dence yet for the relevance of cross-dressing, showing in mice that this process is required for an effective antiviral response.

Humans possess some 100 billion versions of killer (cytotoxic) T cells, each of which carries a T-cell receptor on its cell membrane that recognizes a specific set of antigens. Anti-genic peptides of 8–10 residues are presented to T cells as complexes with MHC class I mol-ecules of the immune system. Unnecessary T-cell responses can gravely damage the host by triggering autoimmune effects, so safe-guards are in place to prevent this. The most important safeguard is that naive T cells — those that have not previously been exposed to an antigen — must initially be activated by dendritic cells, a type of antigen-presenting cell. Dendritic cells are present in immune tissues such as the spleen and lymph nodes, and sample the blood and lymphatic system respectively for antigens. They are derived from the bone marrow and specialize in

presenting viral and tumour antigens to T cells. Once activated, T cells replicate at an aston-

ishing speed (a 4–6-hour division time), leading to a 10,000-fold increase in effector-cell numbers within a few days. The effector cells live for weeks, but a subset called memory cells, which constitute only 1% of the cytotoxic T cells in the body, can live for decades. Having run the gauntlet of the activation safeguards as naive cells, memory cells’ safeguards for pre-venting autoimmunity are relaxed, so they can respond more rapidly to an infection. Wakim and Bevan4 report that memory T cells can be activated through cross-dressing.

If viruses infect dendritic cells, the direct presentation of processed viral proteins can efficiently activate T cells (Fig. 1a). Many viruses, however, infect only one or a few cell types. They could therefore potentially avoid recognition by not infecting dendritic cells. To prevent this — and to be able to present tumour antigens — dendritic cells use cross-presentation, whereby they acquire antigens from extracellular fluids through the process of endocytosis, or from infected cells either by engulfing them or by the diffusion of anti-genic peptides through ‘gap junctions’ formed between the cells (Fig. 1b). Cross-presenta-tion seems to be essential for cytotoxic T-cell responses to many viruses5.

Cross-presentation can also occur by a process called trogocytosis — the transfer of cell-membrane patches or individual proteins between cells6,7 (Fig. 1c). This allows antigen presentation by acceptor dendritic cells to occur immediately, without any processing. Such cross-dressing has been demonstrated in proof-of-principle experiments2,3, and Wakim and Bevan confirm that dendritic cells in culture transfer MHC class I–antigen pep-tide complexes by trogocytosis. Nonetheless,

convincingly extending such findings to situ-ations more like those encountered in vivo has remained notoriously difficult. Wakim and Bevan elegantly do just that using chi-maeric mice that had received transplanted bone marrow.

To generate the chimaeric animals, the authors used g-irradiation to destroy short-lived bone-marrow-derived cells — including the resident dendritic cells of the spleen and lymph nodes — in normal mice. They then transferred bone-marrow-derived stem cells to these animals from a variety of genetically manipulated mice. In this way, they could dis-tinguish dendritic cells that generate MHC class I–peptide complexes from dendritic cells presenting the class I–peptide complexes to T cells. This revealed that cross-dressed dendritic cells (cells that had acquired the complexes) have a crucial role in activating memory, but not naive, T cells.

How can this selectivity be explained? One possibility is that memory T cells specifically interact with a subset of dendritic cells that are specialized for cross-dressing-based activa-tion. Although Wakim and Bevan show that, in

a Direct presentation

b Cross-presentation

c Cross-dressing

Antigen

Infected dendritic cell

Dendritic cellInfected cell

T cell

MHC

Figure 1 | Pathways to antigen presentation. a, Direct presentation occurs when an antigen-presenting cell such as a dendritic cell is infected, and displays processed antigenic peptides in complex with MHC class I molecules on its surface, thereby activating T cells. b, In cross-presentation, dendritic cells acquire antigens obtained by infected cells through endocytosis and phagocytosis, and — with or without some processing — load them onto class I molecules for presentation to T cells. c, In a third pathway, called cross-dressing, dendritic cells acquire preformed MHC class I molecules in complex with antigens from other cells by the process of trogocytosis or through gap junctions. Wakim and Bevan4 show that cross-dressing is used to activate memory T cells, but not naive T cells, in response to viral infection.

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