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Wen Yin,* Si-Qi Zhang,* Wen-Lin Pang,* Xiao-Jiao Chen, Jing Wen, Jiong Hou, Cui Wang, Li-Yun Song, Zhen-Ming Qiu, Peng-Tao Liang, Jia-Li Yuan, Zhong-Shan Yang, Yao Bian Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong-Shan Yang; Yao Bian, Yunnan University of Chinese Medicine, Kunming, Yunnan, People’s Republic of China, Tel +86-871-65919932, Email yangzhongshan@ynutcm.edu.cn; 1345538930@qq.comPurpose: Type 2 diabetes mellitus (T2DM) is a complex genetic disease associated with genetic and environmental factors. Previous studies have shown that changes in the gut microbiota may affect the development of host metabolic diseases and promote the progression of T2DM. Tang-ping-san (TPS) decoction can effectively treat T2DM. However, its specific mechanisms must be evaluated.Patients and Methods: In the present study, we established an animal model of T2DM using a high‑fat diet (HFD) with intraperitoneal injection streptozotocin injection.Results: The therapeutic effect of TPS decoction on T2DM in mice was initially evaluated. TPS decoction was found to improve hyperglycemia, hyperlipidemia, insulin resistance, and pathological liver, pancreatic, and colon changes. Moreover, it reduced the pro-inflammatory cytokine levels. Based on 16SrRNA sequencing, TPS decoction reduced the Firmicutes/Bacteroidetes ratio at the phylum level. At the genus level, it increased the relative abundances of Akkermansia, Muribaculaceae, and the Eubacterium coprostanoligenes group and decreased the relative abundance of Fusobacterium, Escherichia coli, Dubosiella, and Helicobacter.Conclusion: TPS decoction improves T2DM and liver function and reduces the risk of hyperglycemia, hyperlipidemia, insulin resistance, pathological organ changes, and inflammatory reactions. The mechanism of TPS decoction in T2DM can be correlated with the reversal of gut microbiota dysfunction and repair of the intestinal mucosal barrier.Keywords: type 2 diabetes mellitus, tang-ping-san decoction, gut microbiota, glycolipid metabolism, insulin resistance

Emission of harmful gases, nitrogen oxides (NOx), and dioxins pose a serious threat to the human environment; so, it is urgent to control NOx and dioxin emissions. The new regulations for municipal solid waste incineration emissions set new stringent requirements for NOx and dioxin emission standards. Most of the existing pollutant control technologies focus on single-unit NOx reduction or dioxin degradation. However, the installation of separate NOx and dioxins removal units is space-consuming and costs a lot. Nowadays, the simultaneous elimination of NOx and dioxins in the same facility has been regarded as a promising technology. Due to the extremely high toxicity of dioxins, the less toxic chlorobenzene, which has the basic structure of dioxins, has been commonly used as a model molecule for dioxins in the laboratory. In this review, the catalysts used for nitrogen oxides/chlorobenzene (NOx/CB) co-removal were classified into two types: firstly, non-loaded and loaded transition metal catalysts, and their catalytic properties were summarized and outlined. Then, the interaction of the NH3-SCR reaction and chlorobenzene catalytic oxidation (CBCO) on the catalyst surface was discussed in detail. Finally, the causes of catalyst deactivation were analyzed and summarized. Hopefully, this review may provide a reference for the design and commercial application of NOx/CB synergistic removal catalysts.

Recombination between homeologous chromosomes, also known as homeologous exchange (HE), plays a significant role in shaping genome structure and gene expression in interspecific hybrids and allopolyploids of several plant species. However, the molecular mechanisms that govern HEs are not well understood. Here, we studied HE events in the progeny of a nascent allotetraploid (genome AADD) derived from two diploid progenitors of hexaploid bread wheat using cytological and whole-genome sequence analyses. In total, 37 HEs were identified and HE junctions were mapped precisely. HEs exhibit typical patterns of homologous recombination hotspots, being biased toward low-copy, subtelomeric regions of chromosome arms and showing association with known recombination hotspot motifs. But, strikingly, while homologous recombination preferentially takes place upstream and downstream of coding regions, HEs are highly enriched within gene bodies, giving rise to novel recombinant transcripts, which in turn are predicted to generate new protein fusion variants. To test whether this is a widespread phenomenon, a dataset of high-resolution HE junctions was analyzed for allopolyploid Brassica , rice, Arabidopsis suecica , banana, and peanut. Intragenic recombination and formation of chimeric genes was detected in HEs of all species and was prominent in most of them. HE thus provides a mechanism for evolutionary novelty in transcript and protein sequences in nascent allopolyploids.

Polyploidy is a prominent route to speciation in plants; however, this entails resolving the challenges of meiotic instability facing abrupt doubling of chromosome complement. This issue remains poorly understood. We subjected progenies of a synthetic hexaploid wheat, analogous to natural common wheat, but exhibiting extensive meiotic chromosome instability, to heat or salt stress. We selected stress-tolerant cohorts and generated their progenies under normal condition. We conducted fluorescent in situ hybridization/genomic in situ hybridization-based meiotic/mitotic analysis, RNA-Seq and virus-induced gene silencing (VIGS)-mediated assay of meiosis candidate genes. We show that heritability of stress tolerance concurred with increased euploidy frequency due to enhanced meiosis stability. We identified a set of candidate meiosis genes with altered expression in the stress-tolerant plants vs control, but the expression was similar to that of common wheat (cv Chinese Spring, CS). We demonstrate VIGS-mediated downregulation of individual candidate meiosis genes in CS is sufficient to confer an unstable meiosis phenotype mimicking the synthetic wheat. Our results suggest that heritable regulatory changes of preexisting meiosis genes may be hitchhiked as a spandrel of stress tolerance, which significantly improves meiosis stability in the synthetic wheat. Our findings implicate a plausible scenario that the meiosis machinery in hexaploid wheat may have already started to evolve at its onset stage.

The non-random spatial packing of chromosomes in the nucleus plays a critical role in orchestrating gene expression and genome function. Here, we present a Hi-C analysis of the chromatin interaction patterns in rice (Oryza sativa L.) at hierarchical architectural levels. We confirm that rice chromosomes occupy their own territories with certain preferential inter-chromosomal associations. Moderate compartment delimitation and extensive TADs (Topologically Associated Domains) were determined to be associated with heterogeneous genomic compositions and epigenetic marks in the rice genome. We found subtle features including chromatin loops, gene loops, and off-/near-diagonal intensive interaction regions. Gene chromatin loops associated with H3K27me3 could be positively involved in gene expression. In addition to insulated enhancing effects for neighbor gene expression, the identified rice gene loops could bi-directionally (+/-) affect the expression of looped genes themselves. Finally, web-interleaved off-diagonal IHIs/KEEs (Interactive Heterochromatic Islands or KNOT ENGAGED ELEMENTs) could trap transposable elements (TEs) via the enrichment of silencing epigenetic marks. In parallel, the near-diagonal FIREs (Frequently Interacting Regions) could positively affect the expression of involved genes. Our results suggest that the chromatin packing pattern in rice is generally similar to that in Arabidopsis thaliana but with clear differences at specific structural levels. We conclude that genomic composition, epigenetic modification, and transcriptional activity could act in combination to shape global and local chromatin packing in rice. Our results confirm recent observations in rice and A. thaliana but also provide additional insights into the patterns and features of chromatin organization in higher plants.

Although a distinct karyotype with defined chromosome number and structure characterizes each biological species, it is intrinsically labile. Polyploidy or whole-genome duplication has played a pervasive and ongoing role in the evolution of all eukaryotes, and is the most dramatic force known to cause rapid karyotypic reconfiguration, especially at the initial stage. However, issues concerning transgenerational propagation of karyotypic heterogeneity and its translation to phenotypic diversity in nascent allopolyploidy, at the population level, have yet to be studied in detail. Here, we report a large-scale examination of transgenerationally propagated karyotypic heterogeneity and its phenotypic manifestation in an artificially constructed allotetraploid with a genome composition of AADD, that is, involving two of the three progenitor genomes of polyploid wheat. Specifically, we show that 1) massive organismal karyotypic heterogeneity is precipitated after 12 consecutive generations of selfing from a single euploid founder individual, 2) there exist dramatic differences in aptitudes between subgenomes and among chromosomes for whole-chromosome gain and/or loss and structural variations, 3) majority of the numerical and structural chromosomal variations are concurrent due to mutual contingency and possible functional constraint, 4) purposed and continuous selection and propagation for euploidy over generations did not result in enhanced karyotype stabilization, and 5) extent of karyotypic variation correlates with variability of phenotypic manifestation. Together, our results document that allopolyploidization catalyzes rampant and transgenerationally heritable organismal karyotypic heterogeneity that drives population-level phenotypic diversification, which lends fresh empirical support to the still contentious notion that whole-genome duplication enhances organismal evolvability.

The superior optical properties and adjustable bandgap allows for hybrid halide perovskite quantum dots to be promising photocatalytic materials, but the serious radiative recombination and instability inhibit the improvement of photocatalytic conversion efficiency. Herein, we successfully synthesized the FAPbBr3/A-SiO2 nanocomposites photocatalyst by anchoring formamidinium (FA+, HC(NH2)2+) lead halide perovskite quantum dots on aminated silica spheres to construct the composite photocatalysts via N H chemical bonding. The FAPbBr3/A-SiO2 composites show the significantly enhanced visible-light-driven NO removal activity (70%) compared to the pristine FAPbBr3 (30%) in half an hour at room temperature, revealing that the increased active sites and efficient charge carrier separation contribute to the absorption and activation of reactant molecules. This work would open the new possibilities for improving the photocatalytic ability of perovskite quantum dots.

Summary Many ectotherms hibernate in face of the harsh winter conditions to improve their survival rate. However, the molecular mechanism underlying this process remains unclear. Here, we explored the hibernation mechanism of Chinese alligator using integrative multi-omics analysis. We revealed that (1) the thyroid hormone biosynthesis, nutrition absorption and metabolism, muscle contraction, urinary excretion and immunity function pathways are overall downregulated during hibernation; (2) the fat catabolism is completely suppressed, contrasting with the upregulation of hepatic fatty-acid-transporter CPT1A, suggesting a unique energy-saving strategy that differs from that in hibernating mammals; (3) the hibernation-related genes are not only directly regulated by DNA methylation but also controlled by methylation-dependent transcription networks. In addition, we identified and compared tissue-specific, species-specific, and conserved season-biased miRNAs, demonstrating complex post-transcriptional regulation during hibernation. Our study revealed the genetic and epigenetic mechanisms underlying hibernation in the Chinese alligator and provided molecular insights into the evolution of hibernation regulation., Graphical Abstract, Highlights • Metabolic and physiological pathways are overall suppressed during hibernation • Suppressed fat catabolism with active CPT1A suggests a unique energy-saving strategy • Hibernation-related genes are controlled by methylation-dependent transcription network • miRNAs play complex post-transcriptional regulation roles during hibernation, Biological Sciences; Evolutionary Ecology; Transcriptomics

A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response. However, it is unclear what precise role(s) HLA-E/Qa-1 play in the immune response to Mtb. In this study, we found that murine Qa-1 can bind and present Mtb peptide antigens to CD8+ T effector cells during aerosol Mtb infection. Further, mice lacking Qa-1 (Qa-1-/-) were more susceptible to high-dose Mtb infection compared to wild-type controls, with higher bacterial burdens and increased mortality. The increased susceptibility of Qa-1-/- mice was associated with dysregulated T cells that were more activated and produced higher levels of pro-inflammatory cytokines. T cells from Qa-1-/- mice also had increased expression of inhibitory and apoptosis-associated cell surface markers such as CD94/NKG2A, KLRG1, PD-1, Fas-L, and CTLA-4. As such, they were more prone to cell death and had decreased capacity in promoting the killing of Mtb in infected macrophages. Lastly, comparing the immune responses of Qa-1 mutant knock-in mice deficient in either Qa-1-restricted CD8+ Tregs (Qa-1 D227K) or the inhibitory Qa-1-CD94/NKG2A interaction (Qa-1 R72A) with Qa-1-/- and wild-type controls indicated that both of these Qa-1-mediated mechanisms were involved in suppression of the immune response in Mtb infection. Our findings reveal that Qa-1 participates in the immune response to Mtb infection by presenting peptide antigens as well as regulating immune responses, resulting in more effective anti-Mtb immunity., Author summary The disease tuberculosis (TB) is caused by the microbe Mycobacterium tuberculosis (Mtb), and remains a major public health concern. More research is needed to understand the diverse immune responses against Mtb to develop better vaccines. Mouse Qa-1 and its human counterpart HLA-E are nonclassical MHC I molecules that can activate or inhibit immune responses in a variety of diseases. However, their role during the immune response to Mtb remains unknown. We found that Qa-1 can present Mtb peptides to activate CD8+ T effector cells during aerosol Mtb infection. Further, Mtb-infected mice that lacked Qa-1 (Qa-1-/-) had higher numbers of bacteria and died more often than infected mice that expressed Qa-1 (Qa-1+/+). The lack of Qa-1 results in over-activation of the immune response upon infection, which is less efficient in controlling Mtb. Using mice expressing different mutant forms of Qa-1, we showed that Qa-1 can regulate immune responses against Mtb through the interaction with inhibitory CD94/NKG2A receptors as well as the activation of regulatory CD8+ T cells. We believe our study sheds light on the diverse mechanisms at play in generating protective immune responses against Mtb and will inform future mouse and human studies.

Polyploidy or whole-genome duplication is recurrent in plant evolution, yet only a small fraction of whole-genome duplications has led to successful speciation. A major challenge in the establishment of nascent polyploids is sustained karyotype instability, which compromises fitness. The three putative diploid progenitors of bread wheat, with AA, SS (S ∼ B), and DD genomes occurred sympatrically, and their cross-fertilization in different combinations may have resulted in fertile allotetraploids with various genomic constitutions. However, only SSAA or closely related genome combinations have led to the speciation of tetraploid wheats like Triticum turgidum and Triticum timopheevii. We analyzed early generations of four newly synthesized allotetraploid wheats with genome compositions S(sh)S(sh)A(m)A(m), S(l)S(l)AA, S(b)S(b)DD, and AADD by combined fluorescence and genomic in situ hybridization-based karyotyping. Results of karyotype analyses showed that although S(sh)S(sh)A(m)A(m) and S(l)S(l)AA are characterized by immediate and persistent karyotype stability, massive aneuploidy and extensive chromosome restructuring are associated with S(b)S(b)DD and AADD in which parental subgenomes showed markedly different propensities for chromosome gain/loss and rearrangements. Although compensating aneuploidy and reciprocal translocation between homeologs prevailed, reproductive fitness was substantially compromised due to chromosome instability. Strikingly, localized genomic changes in repetitive DNA and copy-number variations in gene homologs occurred in both chromosome stable lines, S(sh)S(sh)A(m)A(m) and S(l)S(l)AA. Our data demonstrated that immediate and persistent karyotype stability is intrinsic to newly formed allotetraploid wheat with genome combinations analogous to natural tetraploid wheats. This property, coupled with rapid gene copy-number variations, may have laid the foundation of tetraploid wheat establishment.

H2-M3–restricted T cells have a preactivated surface phenotype, rapidly expand, and produce cytokines upon stimulation, and, as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8αβ coreceptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although invariant NKT cells are also innate T cells, they are selected exclusively on hematopoietic cells (HC), whereas M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells. Moreover, their phenotypes differ depending on what cells mediate their selection. Although there is a clear correlation between selection on HC and development of innate phenotype, the underlying mechanism remains unclear. Signaling lymphocyte activation molecule-associated protein (SAP) is required for the development of invariant NKT cells and mediates signals from signaling lymphocyte activation molecule receptors that are exclusively expressed on HC. Based on their dual selection pathway, M3-restricted T cells present a unique model for studying the development of innate T cell phenotype. Using both polyclonal and transgenic mouse models, we demonstrate that although M3-restricted T cells are capable of developing in the absence of SAP, SAP is required for HC-mediated selection, development of preactivated phenotype, and heightened effector functions of M3-restricted T cells. These findings are significant because they directly demonstrate the need for SAP in HC-mediated acquisition of innate T cell phenotype and suggest that, due to their SAP-dependent HC-mediated selection, M3-restricted T cells develop a preactivated phenotype and an intrinsic ability to proliferate faster upon stimulation, allowing for an important role in the early response to infection.

Blood coagulation often accompanies bacterial infections and sepsis and is generally accepted as a consequence of immune responses. Though many bacterial species can directly activate individual coagulation factors, they have not been shown to directly initiate the coagulation cascade that precedes clot formation. Here we demonstrated, using microfluidics and surface patterning, that the spatial localization of bacteria substantially affects coagulation of human and mouse blood and plasma. Bacillus cereus and Bacillus anthracis, the anthrax-causing pathogen, directly initiated coagulation of blood in minutes when bacterial cells were clustered. Coagulation of human blood by B. anthracis required secreted zinc metalloprotease InhA1, which activated prothrombin and factor X directly (not via factor XII or tissue factor pathways). We refer to this mechanism as ‘quorum acting’ to distinguish it from quorum sensing—it does not require a change in gene expression, it can be rapid and it can be independent of bacterium-to-bacterium communication.

Adhesion-related complications after abdominal surgery bring out momentous morbidity and costs. Outcomes from animal experiments investigating prevention of adhesions are limited due to lack of consistency in existing animal models. Different intraperitoneal adhesion models were compared the inter observer variability was evaluated to seek for best model. Forty male SD rats weighting 250-300g were included and assigned randomly to four groups with diverse techniques, (A) postoperative adhesion cecum rat model abraded with sterile rasp; (B) postoperative adhesion cecum rat model abraded with sterile dry gauze; (C) postoperative adhesion cecum rat model abraded with sterile blade; (D) postoperative adhesion cecum rat model abraded with vascular clamp. Macroscopic adhesion scores were evaluated by Bigatti scoring system, and the incidence of adhesion were surveyed on the 7th day after the surgery. The results showed that four techniques currently used Bigatti adhesion scoring system are subjective, the sterile rasp is the most consistent and reproducible tool to establish an intraperitoneal adhesion model which is helpful for related studies and the development of new substances for adhesion prevention in the future.

This study was undertaken to observe the characteristics of blood pressure variability (BPV) and sepsis and to investigate changes in blood pressure and its value on the severity of illness in patients with sepsis.Blood parameters, APACHE II score, and 24-hour ambulatory BP were analyzed in 89 patients with sepsis.In patients with APACHE II score19, the values of systolic blood pressure (SBPV), diasystolic blood pressure (DBPV), non-dipper percentage, cortisol (COR), lactate (LAC), platelet count (PLT) and glucose (GLU) were significantly higher than in those with APACHE II score ≤19 (P0.05), whereas the values of procalcitonin (PCT), white blood cell (WBC), creatinine (Cr), PaO2, C-reactive protein (CRP), adrenocorticotropic hormone (ACTH) and tumor necrosis factor α (TNF-α) were not statistically significant (P0.05). Correlation analysis showed that APACHE II scores correlated significantly with SBPV and DBPV (P0.01, r=0.732 and P0.01, r=0.762). SBPV and DBPV were correlated with COR (P=0.018 and r=0.318; P=0.008 and r=0.353 respectively). However, SBPV and DBPV were not correlated with TNF-α, IL-10, and PCT (P0.05). Logistic regression analysis of SBPV, DBPV, APACHE II score, and LAC was used to predict prognosis in terms of survival and non-survival rates. Receiver operating characteristics curve (ROC) showed that DBPV was a better predictor of survival rate with an AUC value of 0.890. However, AUC of SBPV, APACHE II score, and LAC was 0.746, 0.831 and 0.915, respectively.The values of SBPV, DBPV and non-dipper percentage are higher in patients with sepsis. DBPV and SBPV can be used to predict the survival rate of patients with sepsis.

A case of acute renal failure after consumption of fish gall bladder as traditional medical remedy is reported. The patient fully recovered with conservative treatment. The risk of acute kidney failure and even multiple organ dysfunction syndrome following ingestion of fish gall bladder is highlighted.

Allopolyploidization has been a driving force in plant evolution. Formation of common wheat ( Triticum aestivum L.) represents a classic example of successful speciation via allopolyploidy. Nevertheless, the immediate chromosomal consequences of allopolyploidization in wheat remain largely unexplored. We report here an in-depth investigation on transgenerational chromosomal variation in resynthesized allohexaploid wheats that are identical in genome constitution to common wheat. We deployed sequential FISH, genomic in situ hybridization (GISH), and homeolog-specific pyrosequencing, which enabled unequivocal identification of each of the 21 homologous chromosome pairs in each of >1,000 individual plants from 16 independent lines. We report that whole-chromosome aneuploidy occurred ubiquitously in early generations (from selfed generation S 1 to >S 20 ) of wheat allohexaploidy although at highly variable frequencies (20–100%). In contrast, other types of gross structural variations were scant. Aneuploidy included an unexpected hidden type, which had a euploid chromosome number of 2 n = 42 but with simultaneous loss and gain of nonhomeologous chromosomes. Of the three constituent subgenomes, B showed the most lability for aneuploidy, followed by A, but the recently added D subgenome was largely stable in most of the studied lines. Chromosome loss and gain were also unequal across the 21 homologous chromosome pairs. Pedigree analysis showed no evidence for progressive karyotype stabilization even with multigenerational selection for euploidy. Profiling of two traits directly related to reproductive fitness showed that although pollen viability was generally reduced by aneuploidy, the adverse effect of aneuploidy on seed-set is dependent on both aneuploidy type and synthetic line.

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules., Author Summary Tuberculosis, the disease caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden. As T cells are crucial to the control of Mtb infection, it is imperative to decipher the role of different T cell subsets in anti-Mtb immunity for the development of more effective vaccines. While the contribution of conventional T cells to protective immunity against Mtb is well established, the involvement of unconventional T cells is less clear. In this study, we used mutant mice that lack distinct MHC I molecules to characterize immune responses mediated by unconventional T cells during Mtb infection. We found that unconventional CD8+ T cells preferentially expanded in the lung after Mtb infection. These CD8+ T cells responded to numerous mycobacterial antigens, produced multiple cytokines, and contributed to protection against Mtb. A large proportion of unconventional T cells induced by Mtb infection are Qa-2 restricted CD8+ T cells, suggesting this group of T cells may play a greater role in anti-mycobacterial immunity than other unconventional T cell populations that have been characterized previously. Targeting these unconventional T cells may facilitate the design of TB vaccines that are universally effective in ethnically diverse populations due to the non-polymorphic nature of MHC Ib molecules.