T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers1–5. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition6–10. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.

Abstract. A large number of oxygenated organic chemicals (peroxyacyl nitrates, alkyl nitrates, acetone, formaldehyde, methanol, methylhydroperoxide, acetic acid and formic acid) were measured during the 1997 Subsonic Assessment (SASS) Ozone and Nitrogen Oxide Experiment (SONEX) airborne field campaign over the Atlantic. In this paper, we present a first picture of the distribution of these oxygenated organic chemicals (Ox-organic) in the troposphere and the lower stratosphere, and assess their source and sink relationships. In both the troposphere and the lower stratosphere, the total atmospheric abundance of these oxygenated species (ZOx-organic) nearly equals that of total nonmethane hydrocarbons (ZNMHC), which have been traditionally measured.

We examine the ozone production efficiency in transpacific Asian pollution plumes, and the implications for ozone air quality in California, by using aircraft and surface observations in April–May 2002 from the Intercontinental Transport and Chemical Transformation 2002 (ITCT 2K2) campaign off the California coast and the Pacific Exploration of Asian Continental Emission–B (PEACE‐B) campaign over the northwest Pacific. The observations are interpreted with a global three‐dimensional chemical transport model (GEOS‐CHEM). The model reproduces the mean features observed for CO, reactive nitrogen oxides (NOy), and ozone but underestimates the strong (∼20 ppbv) stratospheric contribution to ozone in the middle troposphere. The ITCT 2K2 aircraft sampled two major transpacific Asian pollution plumes, one on 5 May at 5–8 km altitude with CO up to 275 ppbv but no elevated ozone and one on 17 May at 2.5–4 km altitude with CO up to 225 ppbv and ozone up to 90 ppbv. We show that the elevated ozone in the latter plume is consistent with production from peroxyacetylnitrate (PAN) decomposition during subsidence of the plume over the northeast Pacific. This production is particularly efficient because of the strong radiation and low humidity of the subsiding environment. We argue that such PAN decomposition represents a major and possibly dominant component of the ozone enhancement in transpacific Asian pollution plumes. Strong dilution of Asian pollution plumes takes place during entrainment in the U.S. boundary layer, greatly reducing their impact at U.S. surface sites. California mountain sites are more sensitive to Asian pollution because of their exposure to the free troposphere. Model results indicate a mean Asian pollution enhancement of 7 ppbv ozone at Sequoia National Park in May 2002 on those days when the 8‐hour average ozone concentration exceeded 80 ppbv.

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Abstract. Atmospheric hydrogen peroxide (H 2 O 2 ) and organic hydroperoxides were measured from 18 to 30 July in 2006 during the PRIDE-PRD'06 campaign at Backgarden, a rural site located 48 km north of Guangzhou, a mega-city in southern China. A ground-based instrument was used as a scrubbing coil collector to sample ambient air, followed by on-site analysis by high-performance liquid chromatography (HPLC) coupled with post-column derivatization and fluorescence detection. The H 2 O 2 mixing ratio over the 13 days ranged from below the detection limit to a maximum of 4.6 ppbv, with a mean (and standard deviation) of (1.26±1.24) ppbv during the daytime (08:00-20:00 LT). Methyl hydroperoxide (MHP), with a maximum of 0.8 ppbv and a mean (and standard deviation) of (0.28±0.10) ppbv during the daytime, was the dominant organic hydroperoxide. Other organic peroxides, including bis-hydroxymethyl hydroperoxide (BHMP), peroxyacetic acid (PAA), hydroxymethyl hydroperoxide (HMHP), 1-hydroxy-ethyl hydroperoxide (1-HEHP) and ethyl hydroperoxide (EHP), were detected occasionally. The concentration of H 2 O 2 exhibited a pronounced diurnal variation on sunny days, with a peak mixing ratio in the afternoon (12:00-18:00 LT), but lacked an explicit diurnal cycle on cloudy days. Sometimes a second peak mixing ratio of H 2 O 2 was observed during the evening, suggesting that H 2 O 2 was produced by the ozonolysis of Correspondence to: Z. M. Chen (zmchen@pku.edu.cn) alkenes. The diurnal variation profile of MHP was, in general, consistent with that of H 2 O 2 . The estimation indicated that in the morning the H 2 O 2 detected was formed mostly through local photochemical activity, with the rest probably attributable to vertical transport. It is notable that relatively high levels of H 2 O 2 and MHP were found in polluted air. The unexpectedly high level of HO 2 radicals detected in this region can account for the production of hydroperoxides, while the moderate level of NO x suppressed the formation of hydroperoxides. High concentrations of hydroperoxides were detected in samples of rainwater collected in a heavy shower on 25 July when a typhoon passed through, indicating that a considerable mixing ratio of hydroperoxides, particularly MHP, resided above the boundary layer, which might be transported on a regional scale and further influence the redistribution of HO x and RO x radicals. It was found that hydroperoxides, in particular H 2 O 2 , play an important role in the formation of secondary sulfate in the aerosol phase, where the heterogeneous reaction might contribute substantially. A negative correlation between hydroperoxides and water-soluble organic compounds (WSOC), a considerable fraction of the secondary organic aerosol (SOA), was observed, possibly providing field evidence for the importance of hydroperoxides in the formation of SOA found in previous laboratory studies. We suggest that hydroperoxides act as an important link between sulfate and organic aerosols, which needs further study and should be considered in cu...