Find research datasets worth reusing
Search datasets from major research repositories and use ShareScore to quickly assess how well each record supports discovery, access, and reuse.
444
datasets available to search
ShareScore release 0.7.1
Dataset results
444 results for “MHC”
Dataset of "Chronic TCR-MHC (self)-interactions limit the functional potential of TCR affinityincreased CD8 T lymphocytes"
<p><strong>Background</strong>: Affinity-optimized T cell receptor (TCR)-engineered lymphocytes targeting tumor antigens can mediate potent antitumor responses in cancer patients, but also bear substantial risks for off-target toxicities. Most preclinical studies have focused on T cell responses to antigen-specific stimulation. In contrast, little is known on the regulation of T cell responsiveness through continuous TCR triggering and consequent tonic signaling. Here, we addressed the question whether increasing the TCR affinity can lead to chronic interactions occurring directly between TCRs and MHC-(self) molecules, which may modulate the overall functional potency of tumor-redirected CD8 T cells. For this purpose, we developed two complementary human CD8 T cell models (i.e. HLA-A2 knock-in and knock-out) engineered with incremental-affinity TCRs to the HLA-A2/NY-ESO-1 tumor antigen.<br> <strong>Methods</strong>: The impact of HLA-A2 recognition, depending on TCR affinity, was assessed at the levels of the TCR/CD3 complex, regulatory receptors, and signaling, under steady-state conditions and in kinetic studies. The quality of<br> CD8 T cell responses was further evaluated by gene expression and multiplex cytokine profiling, as well as real-time quantitative cell killing, combined with co-culture assays.<br> <strong>Results</strong>: We found that HLA-A2 per se (in absence of cognate peptide) can trigger chronic activation followed by a tolerance-like state of tumor-redirected CD8 T cells with increased-affinity TCRs. HLA-A2pos but not HLA-A2neg T cells displayed an activation phenotype, associated with enhanced upregulation of c-CBL and multiple inhibitory receptors. T cell activation preceded TCR/CD3 downmodulation, impaired TCR signaling and functional<br> hyporesponsiveness. This stepwise activation-to-hyporesponsive state was dependent on TCR affinity and already detectable at the upper end of the physiological affinity range (KD ≤ 1 μM). Similar findings were made when<br> affinity-increased HLA-A2neg CD8 T cells were chronically exposed to HLA-A2pos-expressing target cells.<br> <strong>Conclusions</strong>: Our observations indicate that sustained interactions between affinity-increased TCR and self-MHC can directly adjust the functional potential of T cells, even in the absence of antigen-specific stimulation. The<br> observed tolerance-like state depends on TCR affinity and has therefore potential implications for the design of affinity-improved TCRs for adoptive T cell therapy, as several engineered TCRs currently used in clinical trials share<br> similar affinity properties.</p>
Code for: MHC Heterozygosity Prunes the Numbers of Different T Cell Receptors Expressed in CD4 T Cells
<p>Contains source data file and code for publication "MHC Heterozygosity Prunes the Numbers of Different T Cell Receptors Expressed in CD4 T Cells".<br>Associated FASTQ files are deposited on the NIH SRA under accession: PRJNA1106276</p>
Tumor MHC Class I Expression Associates with Interleukin-2 Response in Melanoma
<p>The processed multiplexed IF data and sample ID corresponding to the raw data in record (https://zenodo.org/record/4300912#.Y-WGBuzMKY-). All code used to produce the results of this study are available at <a href="https://github.com/cBio-MSKCC/Halo_Melanoma_IL2">https://github.com/cBio-MSKCC/Halo_Melanoma_IL2</a>.</p>
High MHC gene copy number maintains diversity despite homozygosity in a Critically Endangered single-island endemic bird, but no evidence of MHC-based mate choice
<p>Raw sequence data from two amplicon libraries of MHC class I exon 3 of Raso Lark <em>Alauda razae</em>, sequenced on an Illumina Miseq. The two different libraries (two different Illumina runs) are collected in separat tar archive (.tar). Within each of those are individual sequence reads as gzipped fastq files (.fastq.gz). Each sample has two files, one for read 1 (R1) and one for read 2 (R2), with file names structured as follows. Delimited by underscore (_) are:</p> <ol> <li>sample name as referred to in the data and paper (“RingNo” in the Supporting data table);</li> <li>formal ID (also referred to in data table, often corresponding to full ring number);</li> <li>Illumina sample number (i.e. based on the order that samples are listed in the sample sheet);</li> <li>Illumina lane number (static as L001, as Miseq instruments have a single lane on their flow cells);</li> <li>read number (R1 [forward] or R2 [reverse]);</li> <li>static identifier from Illumina (001).</li> </ol> <p>Thus, the file 83304_TJ83304_S163_L001_R2_001.fastq.gz is the reverse (read 2) MHC class I exon 3 sequence of individual 83304 (ring number TJ83304).</p>
Data from: Only rare classical MHC-I alleles are highly expressed in the European house sparrow
<p>The exceptional polymorphism observed within genes of the major histocompatibility complex (MHC), a core component of the vertebrate immune system, has long fascinated biologists. The highly polymorphic <em>classical</em> MHC class-I (MHC-I) genes are maintained by pathogen-mediated balancing selection (PMBS), as shown by many sites subject to positive selection, while the more monomorphic MHC-I genes show signatures of purifying selection. In line with PMBS, at any point in time, rare classical MHC alleles are more likely than common classical MHC alleles to confer a selective advantage in host-pathogen interactions. Combining genomic and expression data from the blood of wild house sparrows <em>Passer domesticus</em>, we found that only rare classical MHC-I alleles were highly expressed, while common classical MHC-I alleles were lowly expressed or not expressed. Moreover, highly expressed rare classical MHC-I alleles had more positively selected sites, indicating exposure to stronger PMBS, compared with lowly expressed classical alleles. As predicted, the level of expression was unrelated to allele frequency in the monomorphic non-classical MHC-I alleles. Going beyond previous studies, we offer a fine-scale view of selection on classical MHC-I genes in a wild population by revealing differences in the strength of PMBS according to allele frequency and expression level.</p>
Data from: Response to MHC-based olfactory cues in a mate choice context in two species of darter (Percidae: Etheostoma)
<p>Mate choice is hypothesized to play an important role in maintaining high diversity at major histocompatibility complex (MHC) genes in vertebrates. Many studies have revealed that females across taxa prefer the scent of males with MHC genotypes different to their own. In this study we tested the "opposites-attract" hypothesis in two species of darter with known differences in female criteria used in mate choice: in the fantail darters (a paternal-care species), females prefer males with visual traits related to nest guarding and egg tending, while in rainbow darters (not a paternal-care species) female mate choice criteria are unknown. In dichotomous mate-choice trials, we presented females of both species with the scents of conspecific males with MHC class IIb genotypes that were either similar or dissimilar to that of the focal female. We evaluated the proportion of time each female spent with each male and calculated the average strength of female preference for both species. Female fantail darters demonstrated a preference for the scent of males with similar (rather than dissimilar) MHC genotypes, but this result was not statistically significant. Rainbow darter females showed no preference for the scent of males with similar or dissimilar MHC genotypes. Our results do not support the "opposites-attract" hypothesis in darters.</p>
Structure of an MHC I–tapasin–ERp57 editing complex defines chaperone promiscuity
<p>Adaptive immunity depends on cell surface presentation of antigenic peptides by major histocompatibility complex class I (MHC I) molecules and on stringent ER quality control in the secretory pathway. The chaperone tapasin in conjunction with the oxidoreductase ERp57 is crucial for MHC I assembly and for shaping the epitope repertoire for high immunogenicity. However, how the tapasin–ERp57 complex engages MHC I clients has not yet been determined at atomic detail. Here, we present the 2.7 Å crystal structure of a tapasin–ERp57 heterodimer in complex with peptide-receptive MHC I. Our study unveils molecular details of client recognition by the multichaperone complex and highlights elements indispensable for peptide proofreading. The structure of this transient ER quality control complex provides the mechanistic basis for the selector function of tapasin and showcases how the numerous MHC I allomorphs are chaperoned during peptide loading and editing.</p>
TCR-MHC Germline Interaction Scores Generated Using AIMS
<p>These data were generated using the AIMS interaction scoring function as outlined in the manuscript "A Systematic Characterization of Germline-Encoded Contacts Identifies the Source of Bias in TCR-MHC Interactions". They accompany the AIMS version 0.7 software available on GitHub: https://github.com/ctboughter/AIMS . These files are meant to be loaded into the mhc_germline_analysis.ipynb file, but are too large to be included on the GitHub page itself.</p>
Relationship between genome-wide and MHC class I and II genetic diversity and complementarity in a nonhuman primate
<p>Although mate choice is expected to favor partners with advantageous genetic properties, the relative importance of genome-wide characteristics, such as overall heterozygosity or kinship, versus specific loci, is unknown. To disentangle genome-wide and locus-specific targets of mate choice, we must first understand congruence in global and local variation within the same individual. This study compares genetic diversity, both absolute and relative to other individuals (e.g., complementarity), assessed across the genome to that found at the major histocompatibility complex (MHC), a hyper-variable gene family integral to immune system function and implicated in mate choice across species. Using DNA from 22 captive olive baboons (<em>Papio anubis</em>), we conducted double digest restriction-site associated DNA sequencing to estimate genome-wide heterozygosity and kinship and sequenced two class I and two class II MHC loci. We found that genome-wide diversity was not associated with MHC diversity, and that diversity at class I MHC loci was not correlated with diversity at class II loci. Additionally, kinship was a significant predictor of the number of MHC alleles shared between dyads at class II loci. Our results provide further evidence of the strong selective pressures maintaining genetic diversity at the MHC in comparison to other randomly selected sites throughout the genome. Furthermore, our results indicate that class II MHC disassortative mate choice may mediate inbreeding avoidance in this population. Our study suggests that mate choice favoring genome-wide genetic diversity is not always synonymous with mate choice favoring MHC diversity, and highlights the importance of controlling for kinship when investigating MHC-associated mate choice.</p>
Alternative splicing and genetic variation of MHC-E: Implications for rhesus cytomegalovirus-based vaccines
<p>We used long-read sequencing to interrogate rhesus macaque (RM) MHC-E (Mamu-E) alternative splicing and genetic variations. Full-length Mamu-E RNA isoforms were recovered using the PacBio Iso-Seq method. Incomplete 5' ends of Mamu-E isoforms were confirmed using Sanger sequencing, where we identified three additional isoforms. Full-length human MHC-E (HLA-E) isoforms were also recovered using the PacBio Iso-Seq method. Isoform sequences and annotations are provided for both Mamu-E and HLA-E in addition to Mamu-E Sanger sequencing data. HLA-E annotations are reported using the hg38 reference, while Mamu-E annotations are shown using rhesus MHC Class I and II assemblies previously generated using Bacterial Artificial Cloning (BAC) technology (https://www.ncbi.nlm.nih.gov/nuccore/AC148696.1).</p> <p>Using PacBio Long Amplicon Analysis, we sequenced complete Mamu-E coding regions of 59 RMs and additionally captured 3' UTR polymorphism using mRNA-seq haplotype phasing analysis. The complete genotyping data for these animals are provided as well as animal metadata. Genotyping data is shown using the Mamu-E canonical isoform (Mamu-E1 from Iso-Seq analysis) as reference.</p>
Computationally profiling peptide:MHC recognition by T-cell receptors and T-cell receptor-mimetic antibodies
<p>Supporting datasets for preprint version of "Computationally profiling peptide:MHC recognition by T-cell receptors and T-cell receptor-mimetic antibodies".</p>
Correlated evolution of oxidative physiology and MHC-based immunosurveillance in birds
<p>Maintenance and activation of the immune system incurs costs, not only in terms of substrates and energy, but also via collateral oxidative damage to host cells or tissues during immune response. So far, associations between immune function and oxidative damage have been primarily investigated at intra-specific scales. Here, we hypothesized that pathogen-driven selection should favour evolution of effective immunosurveillance mechanisms (e.g. Major Histocompatibility Complex, MHC) and antioxidant defences to mitigate oxidative damage resulting from immune function. Using phylogenetically-informed comparative approaches, we provided evidence for correlated evolution of host oxidative physiology and MHC-based immunosurveillance in birds. Species selected for more robust MHC-based immunosurveillance (higher gene copy numbers and allele diversity) showed stronger antioxidant defences, although selection for MHC diversity still showed a positive evolutionary association with oxidative damage to lipids. Our results indicate that historical pathogen-driven selection for highly duplicated and diverse MHC could have promoted the evolution of efficient antioxidant mechanisms, but these evolutionary solutions may be insufficient to keep oxidative stress at bounds. Although the precise nature of mechanistic links between the MHC and oxidative stress remains unclear, our study suggests that a general evolutionary investment in immune function may require co-adaptations at the level of host oxidative metabolism.</p>
Fig. 2. MHC I in Saphonecrus globosus Schweger and Tang 2015
Fig. 2. MHC I isoform distribution and single fiber cross-sectional area (CSA). (A) Representative immunofluorescent images of MHC I (green) fibers in gastrocnemius muscles in each group. Red represents laminin stain of myofiber interstitial tissue. Scale bar = 50 μm. (B) The changes in MHC I isoform distribution (%) in mice and Daurian ground squirrels. (C) The changes in muscle single fiber CSA in mice and Daurian ground squirrels. CON: control mice, OB: mice after 3 months of ingesting high fat diet, SA: summer active Daurian ground squirrels, PRE: pre-hibernation, squirrels that finished natural fattening, sacrificed in late-autumn (end of September, 30–40 d before hibernation). Values are mean ± SEM, n = 6. *p <0.05 compared with CON group.
MHC Motif Atlas CSV
<p>CSV Format of MHC Motif Atlas data taken from <a href="http://mhcmotifatlas.org/home">http://mhcmotifatlas.org/home</a></p>
Individual allotype responses to HEK-293T-based cell lines ex-pressing single MHC class I chain-related gene B alleles
<p><span>Figure S1.</span><span> Individual allotype responses between 64 sera collected from kidney transplant patients and 5 single </span><span>MICB</span><span> allele-expressing cell lines established in </span><span>HLA</span><span> class I, </span><span>MICA,</span><span> and </span><span>MICB</span><span>-null HEK-293T cells. </span><span>HLA</span><span> class I, </span><span>MICA,</span><span> and </span><span>MICB</span><span> genes were removed using CRISPR/Cas9 in previous studies [20, 21]. Some of the 64 sera showed responses to single </span><span>MICA</span><span> allele-expressing cell lines [21]. However, none of the 64 sera showed individual allotype responses in this study.</span></p>
Fig. 2 in MHC-associated Baylisascaris schroederi load informs the giant panda reintroduction program
Fig. 2. Effects of MHC genotypes on (a–b) infection probability, (c–d) EPG of B. schroederi using important predictors. The Bars show the 95%CI.
Fig. 3 in MHC-associated Baylisascaris schroederi load informs the giant panda reintroduction program
Fig. 3. Effects of MHC alleles on infection probability (a and b) and EPG (c and d) of B. schroeder.i. The bars show the 95%CI.
Meta-analysis of major histocompatibility complex (MHC) class IIA reveals polymorphism and positive selection in many vertebrate species
<p>Pathogen-mediated selection and sexual selection are important drivers of evolution. Both processes are known to target genes of the major histocompatibility complex (MHC), a gene family encoding cell-surface proteins that display pathogen peptides to the immune system. The MHC is also a model for understanding processes such as gene duplication and trans-species allele sharing. The class II MHC protein is a heterodimer whose peptide-binding groove is encoded by an MHC-IIA gene and an MHC-IIB gene. However, our literature review found that class II MHC papers on infectious disease or sexual selection included IIA data only 18% and 9% of the time, respectively. To assess whether greater emphasis on MHC-IIA is warranted, we analyzed MHC-IIA sequence data from 50 species of vertebrates (fish, amphibians, birds, mammals) to test for polymorphism and positive selection. We found that the number of MHC-IIA alleles within a species was often high, and covaried with sample size and number of MHC-IIA genes assayed. While MHC-IIA variability tended to be lower than that of MHC-IIB, the difference was only ~25%, with ~3 fewer IIA alleles than IIB. Furthermore, the unexpectedly high MHC-IIA variability showed clear signatures of positive selection in most species, and positive selection on MHC-IIA was stronger in fish than in other surveyed vertebrate groups. Our findings underscore that MHC-IIA can be an important target of selection. Future work should therefore expand the characterization of MHC-IIA at both allelic and genomic scales, and incorporate MHC-IIA into models of fitness consequences of MHC variation.</p>
The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I
<p>Adaptive immune responses are triggered by antigenic peptides presented on major histocompatibility complex class I (MHC I) at the surface of pathogen-infected or cancerous cells. Formation of stable peptide-MHC I complexes is facilitated by tapasin and TAPBPR, two related MHC I-specific chaperones that catalyze selective loading of suitable peptides onto MHC I in a process called peptide editing or proofreading. On their journey to the cell surface, MHC I complexes must pass a quality control step performed by UGGT1, which senses the folding status of the transiting N-linked glycoproteins in the endoplasmic reticulum (ER). UGGT1 reglucosylates non-native glycoproteins and thereby allows them to revisit the ER folding machinery. Here, we describe a reconstituted <em>in-vitro</em> system of purified human proteins that enabled us to delineate the function of TAPBPR during the UGGT1-catalyzed quality control and reglucosylation of MHC I. By combining glycoengineering with liquid chromatography-mass spectrometry, we show that TAPBPR promotes reglucosylation of peptide-free MHC I by UGGT1. Thus, UGGT1 cooperates with TAPBPR in fulfilling a crucial function in the quality control mechanisms of antigen processing and presentation.</p>
MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats
<p>Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to infer their zoonotic potential. Members of the cryptic <em>Hipposideros</em> bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC diversity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV-229E, CoV-2B, and CoV-2Bbasal) susceptibility to immunogenetic differences amongst four <em>Hipposideros</em> bat species. From the 2,072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, <em>Hipposideros caffer</em> D, were most infected with CoV-229E and SARS-related CoV-2B. Using a subset of 569 bats we determined that much of the existent allelic and functional (i.e., supertype) MHC DRB class II diversity originated from common ancestry. One MHC supertype shared amongst all species, ST12, was consistently linked to susceptibility with CoV-229E, which is closely related to the common cold agent HCoV-229E, and infected bats with ST12 had a lower body condition. The same MHC supertype was connected to resistance to CoV-2B, and bats with ST12 were less likely be co-infected with CoV-229E and CoV-2B. Our work suggests a role of immunogenetics in determining CoV susceptibility in bats. We advocate for the preservation of functional genetic and species diversity in reservoirs as means of mitigating the risk of disease spillover.</p>
ScienceDex guides
Understand access before you commit
These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.