74 research outputs found
T cell epitope clustering in the highly immunogenic BZLF1 antigen of Epstein-Barr virus
Polymorphism in the human leukocyte antigen (HLA) loci ensures that the CD8 T cell response to viruses is directed against a diverse range of antigenic epitopes, thereby minimizing the impact of virus escape mutation across the population. The BZLF1 antigen of Epstein-Barr virus is an immunodominant target for CD8 T cells, but the response has been characterized only in the context of a limited number of HLA molecules due to incomplete epitope mapping. We have now greatly expanded the number of defined CD8 T cell epitopes from BZLF1, allowing the response to be evaluated in a much larger proportion of the population. Some regions of the antigen fail to be recognized by CD8 T cells, while others include clusters of overlapping epitopes presented by different HLA molecules. These highly immunogenic regions of BZLF1 include polymorphic sequences, such that up to four overlapping epitopes are impacted by a single amino acid variation common in different regions of the world. This focusing of the immune response to limited regions of the viral protein could be due to sequence similarity to human proteins creating "immune blind spots" through self-tolerance. This study significantly enhances the understanding of the immune response to BZLF1, and the precisely mapped T cell epitopes may be directly exploited in vaccine development and adoptive immunotherapy
The immunogenicity of a viral cytotoxic T cell epitope is controlled by its MHC-bound conformation
Thousands of potentially antigenic peptides are encoded by an infecting pathogen; however, only a small proportion induce measurable CD8+ T cell responses. To investigate the factors that control peptide immunogenicity, we have examined the cytotoxic T lymphocyte (CTL) response to a previously undefined epitope (77APQPAPENAY86) from the BZLF1 protein of Epstein-Barr virus (EBV). This peptide binds well to two human histocompatibility leukocyte antigen (HLA) allotypes, HLA-B*3501 and HLA-B*3508, which differ by a single amino acid at position 156 (156Leucine vs. 156Arginine, respectively). Surprisingly, only individuals expressing HLA-B*3508 show evidence of a CTL response to the 77APQPAPENAY86 epitope even though EBV-infected cells expressing HLA-B*3501 process and present similar amounts of peptide for CTL recognition, suggesting that factors other than peptide presentation levels are influencing immunogenicity. Functional and structural analysis revealed marked conformational differences in the peptide, when bound to each HLA-B35 allotype, that are dictated by the polymorphic HLA residue 156 and that directly affected T cell receptor recognition. These data indicate that the immunogenicity of an antigenic peptide is influenced not only by how well the peptide binds to major histocompatibility complex (MHC) molecules but also by its bound conformation. It also illustrates a novel mechanism through which MHC polymorphism can further diversify the immune response to infecting pathogens
An L Band Spectrum of the Coldest Brown Dwarf
The coldest brown dwarf, WISE 0855, is the closest known planetary-mass,
free-floating object and has a temperature nearly as cold as the solar system
gas giants. Like Jupiter, it is predicted to have an atmosphere rich in
methane, water, and ammonia, with clouds of volatile ices. WISE 0855 is faint
at near-infrared wavelengths and emits almost all its energy in the
mid-infrared. Skemer et al. 2016 presented a spectrum of WISE 0855 from 4.5-5.1
micron (M band), revealing water vapor features. Here, we present a spectrum of
WISE 0855 in L band, from 3.4-4.14 micron. We present a set of atmosphere
models that include a range of compositions (metallicities and C/O ratios) and
water ice clouds. Methane absorption is clearly present in the spectrum. The
mid-infrared color can be better matched with a methane abundance that is
depleted relative to solar abundance. We find that there is evidence for water
ice clouds in the M band spectrum, and we find a lack of phosphine spectral
features in both the L and M band spectra. We suggest that a deep continuum
opacity source may be obscuring the near-infrared flux, possibly a deep
phosphorous-bearing cloud, ammonium dihyrogen phosphate. Observations of WISE
0855 provide critical constraints for cold planetary atmospheres, bridging the
temperature range between the long-studied solar system planets and accessible
exoplanets. JWST will soon revolutionize our understanding of cold brown dwarfs
with high-precision spectroscopy across the infrared, allowing us to study
their compositions and cloud properties, and to infer their atmospheric
dynamics and formation processes.Comment: 19 pages, 21 figures. Accepted for publication in Ap
WISEP J180026.60+013453.1: A Nearby Late L Dwarf Near the Galactic Plane
We report a nearby L7.5 dwarf discovered using the Preliminary Data Release
of the Wide-field Infrared Survey Explorer (WISE) and the Two Micron All-Sky
Survey (2MASS). WISEP J180026.60+013453.1 has a motion of 0.42 arcsec/yr and an
estimated distance of 8.8 \pm 1.0 pc. With this distance, it currently ranks as
the sixth closest known L dwarf, although a trigonometric parallax is needed to
confirm this distance. It was previously overlooked because it lies near the
Galactic Plane (b=12). As a relatively bright and nearby late L dwarf with
normal near-infrared colors, W1800+0134 will serve as a benchmark for studies
of cloud-related phenomena in cool substellar atmospheres.Comment: 12 pages, 2 figure, accepted to the Astronomical Journal (AJ
Soil warming alters nitrogen cycling in a New England forest : implications for ecosystem function and structure
© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Oecologia 168 (2012): 819-828, doi:10.1007/s00442-011-2133-7.Global climate change is expected to affect
terrestrial ecosystems in a variety of ways. Some of the
more well-studied effects include the biogeochemical
feedbacks to the climate system that can either increase or
decrease the atmospheric load of greenhouse gases such
as carbon dioxide and nitrous oxide. Less well-studied are
the effects of climate change on the linkages between soil
and plant processes. Here, we report the effects of soil
warming on these linkages observed in a large field
manipulation of a deciduous forest in southern New
England, USA, where soil was continuously warmed 5°C
above ambient for 7 years. Over this period, we have observed significant changes to the nitrogen cycle that
have the potential to affect tree species composition in the
long term. Since the start of the experiment, we have
documented a 45% average annual increase in net nitrogen
mineralization and a three-fold increase in nitrification
such that in years 5 through 7, 25% of the nitrogen
mineralized is then nitrified. The warming-induced
increase of available nitrogen resulted in increases in the
foliar nitrogen content and the relative growth rate of
trees in the warmed area. Acer rubrum (red maple) trees
have responded the most after 7 years of warming, with
the greatest increases in both foliar nitrogen content and
relative growth rates. Our study suggests that considering
species-specific responses to increases in nitrogen availability
and changes in nitrogen form is important in
predicting future forest composition and feedbacks to the
climate system.This work was supported by the National Institute
for Climate Change Research (DOE-DE-FCO2-06-ER64157),
DOE BER (DE-SC0005421) and the Harvard Forest Long-Term
Ecological Research program (NSF-DEB-0620443)
Allelic polymorphism in the T cell receptor and its impact on immune responses
In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01 public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2β loop (Gln55→His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55→Ala55) in complex with HLA-B*3501 revealed that the Gln55→His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection
The Brown Dwarf Kinematics Project (BDKP) I. Proper Motions and Tangential Velocities for a Large Sample of Late-type M, L and T Dwarfs
We report proper motion measurements for 427 late-type M, L and T dwarfs, 332
of which have been measured for the first time. Combining these new proper
motions with previously published measurements yields a sample of 841 M7-T8
dwarfs. We combined parallax measurements or calculated spectrophotometric
distances and computed tangential velocities for the entire sample. We find
that kinematics for the full and volume-limited 20 pc samples are consistent
with those expected for the Galactic thin disk, with no significant differences
between late-type M, L, and T dwarfs. Applying an age-velocity relation we
conclude that the average kinematic age of the 20 pc sample of ultracool dwarfs
is older than recent kinematic estimates and more consistent with age results
calculated with population synthesis models. There is a statistically distinct
population of high tangential velocity sources whose kinematics suggest an even
older population of ultracool dwarfs belonging to either the Galactic thick
disk or halo. We isolate subsets of the entire sample, including low
surface-gravity dwarfs, unusually blue L dwarfs, and photometric outliers in
J-Ks color and investigate their kinematics. We find that the spectroscopically
distinct class of unusually blue L dwarfs has kinematics clearly consistent
with old age, implying that high surface-gravity and/or low metallicity may be
relevant to their spectral properties. The low surface-gravity dwarfs are
kinematically younger than the overall population, and the kinematics of the
red and blue ultracool dwarfs suggest ages that are younger and older than the
full sample, respectively. We also present a reduced proper motion diagram at
2MASS Ks for the entire population and find that a limit of H_Ks > 18 excludes
M dwarfs from the L and T dwarf population regardless of near-infrared color.Comment: Accepted for publication in the Astronomical Journal, 21 pages text,
12 tables, 12 figure
Update of the best practice dietetic management of overweight and obese children and adolescents: a systematic review protocol
To update an existing systematic review series of randomized controlled trials (RCT) that include a dietary intervention for the management of overweight or obesity in children or adolescents.Specifically, the review questions are: In randomized controlled trials of interventions which include a dietary intervention for the management of overweight or obesity in children or adolescents
Astro2020 science white paper:fundamental physics with brown dwarfs: the mass-radius relation
The lowest-mass stars, brown dwarfs and giant exoplanets span a minimum in
the mass-radius relationship that probes the fundamental physics of extreme
states of matter, magnetism, and fusion. This White Paper outlines scientific
opportunities and the necessary resources for modeling and measuring the
mass-radius relationship in this regime.Comment: 7 pages, submitted to Astro2020 Science White Paper cal
Astro2020 science white paper:fundamental physics with brown dwarfs: the mass-radius relation
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