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Correlative CD4 and CD8 T-cell immunodominance in humans and mice:Implications for preclinical testing

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Cellular & Molecular Immunology 2023年第11期20卷 1328-1338页

作者： Tertuliano Alves Pereira Neto John Sidney Alba Grifoni Alessandro Sette Center for infectious disease and Vaccine Research La Jolla Institute for Immunology(LJI)La JollaCA92037USA Department of Medicine Division of Infectious Diseases and Global Public HealthUniversity of CaliforniaSan DiegoLa JollaCA92037USA

Antigen-specific T-cell recognition is restricted by Major Histocompatibility Complex(MHC)molecules,and differences between CD4 and CD8 immunogenicity in humans and animal species used in preclinical vaccine testing are yet to be fully *** this study,we addressed this matter by analyzing experimentally identified epitopes based on published data curated in the Immune Epitopes DataBase(IEDB)*** first analyzed SARS-CoV-2 spike(S)and nucleoprotein(N),which are two common targets of the immune response and well studied in both human and mouse *** observed a weak but statistically significant correlation between human and H-2^(b)mouse T-cell responses(CD8 S specific(r=0.206,p=1.37×10^(−13));CD4 S specific(r=0.118,p=2.63×10^(−5))and N specific(r=0.179,p=2.55×10^(−4))).Due to intrinsic differences in MHC molecules across species,we also investigated the association between the immunodominance of common Human Leukocyte Antigen(Hla)alleles for which Hla transgenic mice are available,namely,A*02:01,B*07:02,DRB1*01:01,and DRB1*04:01,and found higher significant correlations for both CD8 and CD4(maximum r=0.702,p=1.36×10^(−31)and r=0.594,p=3.04−122,respectively).Our results further indicated that some regions are commonly immunogenic between humans and mice(either H-2^(b)or Hla transgenic)but that others are human ***,we noted a significant correlation between CD8 and CD4 S-(r=0.258,p=7.33×10^(21))and N-specific(r=0.369,p=2.43×10^(14))responses,suggesting that discrete protein subregions can be simultaneously recognized by T *** findings were confirmed in other viral systems,providing general guidance for the use of murine models to test T-cell immunogenicity of viral antigens destined for human use.

关键词： T cells SARS-CoV-2 Vaccine Animal testing Hla

Harnessing memory adaptive regulatory T cells to control autoimmunity in type 1 diabetes

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Journal of Molecular Cell Biology 2012年第1期4卷 38-47页

作者： Cheng-Rui Li Bas J.G.Baaten Linda M.Bradley infectious and Inflammatory disease Center Sanford-Burnham Medical Research Institute10901 North Torrey Pines RoadLa JollaCA 92037USA

Type 1 diabetes(T1D)results from autoimmune destruction of insulin-producing b-cells in the pancreatic *** is an immediate need to restore both b-cell function and immune tolerance to control disease progression and ultimately cure ***,there is no effective treatment strategy to restore glucose regulation in patients with ***3-expressing CD4^(+) regulatory T cells(Tregs)are potential candidates to control autoimmunity because they play a central role in maintaining ***,deficiencies in either naturally occurring Tregs(nTregs)themselves and/or their ability to control pathogenic effector T cells have been associated with ***,we hypothesize that nTregs can be replaced by FoxP3^(+) adaptive Tregs(aTregs),which are uniquely equipped to combat autoreactivity in *** nTregs,aTregs are stable and provide long-lived *** this review,we summarize the current understanding of aTregs and their potential for use as an immunological intervention to treat T1D.

关键词： type 1 diabetes adaptive regulatory T cells autoimmunity immunotherapy

Fast and Efficient Root Phenotyping via Pose Estimation

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Plant Phenomics 2024年第2期6卷 477-497页

作者： Elizabeth M.Berrigan Lin Wang Hannah Carrillo Kimberly Echegoyen Mikayla Kappes Jorge Torres Angel Ai-Perreira Erica McCoy Emily Shane Charles D.Copeland lauren Ragel Charidimos Georgousakis Sanghwa Lee Dawn Reynolds Avery Talgo Juan Gonzalez Ling Zhang Ashish B.Rajurkar Michel Ruiz Erin Daniels Liezl Maree Shree Pariyar Wolfgang Busch Talmo D.Pereira Salk institute for Biological Studies La JollaCA 92037USA

Image segmentation is commonly used to estimate the location and shape of plants and their external *** masks are then used to localize landmarks of interest and compute other geometric features that correspond to the plant's *** its prevalence,segmentation-based approaches are laborious(requiring extensive annotation to train)and error-prone(derived geometric features are sensitive to instance mask integrity).

关键词： fast root efficient estimation phenotyping pose

Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch

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Protein & Cell 2019年第6期10卷 395-404页

作者： Daisuke Aki Qian Li Hui Li Yun-Cai Liu Jee Ho Lee institute for Immunology Tsinghua-Peking Center for Life Sciences School of Medicine Tsinghua University Beijing 100084 China la jolla institute for Allergy and Immunology La Jolla CA 92037 USA

Protein ubiquitination is an important means of posttranslational modification which plays an essential role in the regulation of various aspects of leukocyte development and function. The specificity of ubiquitin tagging to a protein substrate is determined by E3 ubiquitin ligases via defined E3-substrate interactions. In this review, we will focus on two E3 ligases, VHL and Itch, to discuss the latest progress in understanding their roles in the differentiation and function of CD4+ T helper cell subsets, the stability of regulatory T cells, effector function of CD8+ T cells, as well as the development and maturation of innate lymphoid cells. The biological implications of these E3 ubiquitin ligases will be highlighted in the context of normal and dysregulated immune responses including the control of homeostasis, inflammation, auto-immune responses and anti-tumor immunity. Further elucidation of the ubiquitin system in immune cells will help in the design of new therapeutic interventions for human immunological diseases and cancer.

关键词： ubiquitin E3ligase VHL HIF Itch WWP2 Cbl-b inflammation autoimmunity

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Connective Tissue Growth Factor Expression in Human Bronchial Epithelial Cells

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Acta Biochimica et Biophysica Sinica 2006年第1期38卷 53-57页

作者： AmritaDOSANJH Department of Molecular and Experimental Medicine the Scripps Research institute USA la jolla 92122

Connective tissue growth factor (CTGF) is a cysteine-rich protein that promotes extracellularmatrix *** is selectively induced by transforming growth factor β and des-Arg kallidin in lungfibroblasts and increases steady-state mRNA levels of α type I collagen,5α-integrin and fibronectin *** epithelial cells have been proposed to functionally interact with lung *** investigated if bronchial epithelial cells are able to synthesize *** bronchial epithelialcells were grown to subconfluence in standard growth *** cells grown in small airwaygrowth media were harvested following starvation for up to 24 *** of CTGF transcripts wasmeasured by *** was also completed using a commercially available *** cells expressed readily detectable CTGF *** of these cells resulted in a quantitativedecline of CTGF *** sequencing of the PCR product identified human ***-tochemistry confirmed intracellular CTGF in the cells and none in negative control *** conclude thatbronchial epithelial cells could be a novel source of *** epithelial cell-derived CTGF could thusdirectly influence the deposition of collagen in certain fibrotic lung diseases.

关键词： bronchial epithelial cell connective tissue growth factor collagen deposition remodeling

Prevention of DNA re-replication in eukaryotic cells

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Journal of Molecular Cell Biology 2011年第1期3卷 13-22页

作者： lan N.Truong Xiaohua Wu Department of Molecular and Experimental Medicine The Scripps Research InstituteLa JollaCA 92037USA

DNA replication is a highly regulated process involving a number of licensing and replication factors that function in a carefully orchestrated manner to faithfully replicate DNA during every cell *** of proper licensing control leads to deregulated DNA replication including DNA re-replication,which can cause genome instability and *** organisms have established several conserved mechanisms to prevent DNA re-replication and to counteract its potentially harmful *** mechanisms include tightly controlled regulation of licensing factors and activation of cell cycle and DNA damage *** licensing control and its associated compromised checkpoints have both been observed in tumor cells,indicating that proper functioning of these pathways is essential for maintaining genome *** this review,we discuss the regulatory mechanisms of licensing control,the deleterious consequences when both licensing and checkpoints are compromised,and present possible mechanisms to prevent re-replication in order to maintain genome stability.

关键词： DNA re-replication cell cycle checkpoints DNA damage response Cdt1 DSB repair genome stability tumorigenesis

Transforming Growth Factor-β Expression Induced by Rhinovirus Infection in Respiratory Epithelial Cells

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Acta Biochimica et Biophysica Sinica 2006年第12期38卷 911-914页

作者： Amrita DOSANJH la jolla 92037 USA Department of Molecular and Experimental Medicine the Scripps Research institute

Rhinovirus infection of the lower airways is now a recognized disease,associated withbronchiolitis and *** bronchial epithelial cells are the host cells when rhinovirus infection occurs inthe *** was hypothesized that a pro-fibrotic growth factor response may occur in these infected cells,leading to production of a key transforming growth factor,TGF-β-*** epithelial cells were inocu-lated with human rhinovirus and compared at day 1,3 and 5 to control non-infected *** culturesupernatant fluid and cellular RNA were *** amount of released TGF-β protein was measured byenzyme-linked immunosorbent assay (ELISA).Expression of TGF-β at the level of transcription was mea-sured by polymerase chain reaction (PCR) and gel *** results show that at all time pointsstudied,TGF-β production is greater in the infected cells,as demonstrated by ELISA (Plammation,or in the setting of persistent asthma,could potentially lead toincreased fibrosis and collagen deposition.

关键词： rhinovirus TGF-β bronchial asthma common cold

Neuroimmune actions in the brain and interactions with the effects of alcohol

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Neural Regeneration Research 2021年第9期16卷 1791-1792页

作者： Donna L.Gruol Neuroscience Department The Scripps Research InstituteLa JollaCAUSA

The neuroimmune system of the brain:Early studies(1990’s)on the neurological consequences of human immunodeficiency virus-1(HIV-1)infection in the brain were instrumental in establishing that specific brain cell types can function as an innate immune system within the brain and in that role influence cognitive function(Kaul et al.,2005).

关键词： Neuroimmune actions in the brain and interactions with the effects of alcohol

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Do viral infections protect from or enhance type 1 diabetes and how can we tell the difference?

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Cellular & Molecular Immunology 2011年第3期8卷 193-198页

作者： Urs Christen Matthias G von Herrath Pharmazentrum Frankfurt/ZAFES Klinikum der Goethe UniversitaätFrankfurt am MainGermany la jolla institute for Allergy and Immunology La JollaCAUSA

Virus infections have been implicated in both initiation of and protection from autoimmune diseases,such as type 1 diabetes(T1D).In this review we intend to reflect on recent evidence how viruses might on the one hand be involved in the pathogenesis of T1D and on the other hand induce a state of protection from autoimmune-mediated *** is important to acknowledge that human individuals encounter more than just one virus infection in their ***,it is important to integrate more than just one possible environmental triggering factor for autoimmune diseases to occur.

关键词： animal model enterovirus hygiene hypothesis molecular mimicry pathogens