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  • 1
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    Differential clustering of CD4 and CD3zeta during T cell recognition (2000)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2000-08-26
    Description: Whereas T helper cells recognize peptide-major histocompatibility complex (MHC) class II complexes through their T cell receptors (TCRs), CD4 binds to an antigen-independent region of the MHC. Using green fluorescent protein-tagged chimeras and three-dimensional video microscopy, we show that CD4 and TCR-associated CD3zeta cluster in the interface coincident with increases in intracellular calcium. Signaling-, costimulation-, and cytoskeleton-dependent processes then stabilize CD3zeta in a single cluster at the center of the interface, while CD4 moves to the periphery. Thus, the CD4 coreceptor may serve primarily to "boost" recognition of ligand by the TCR and may not be required once activation has been initiated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Krummel, M F -- Sjaastad, M D -- Wulfing, C -- Davis, M M -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1349-52.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, and the Howard Hughes Medical Institute, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958781" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD3/*metabolism ; Antigens, CD4/*metabolism ; Calcium Signaling ; Cell Line ; Cytoskeleton/physiology ; Histocompatibility Antigens Class II/immunology/metabolism ; Ligands ; *Lymphocyte Activation ; Microscopy, Video ; Phosphorylation ; Receptors, Antigen, T-Cell/immunology/metabolism ; Recombinant Fusion Proteins/metabolism ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Deletional tolerance mediated by extrathymic Aire-expressing cells (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-08-09
    Description: The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting naive autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532844/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gardner, James M -- Devoss, Jason J -- Friedman, Rachel S -- Wong, David J -- Tan, Ying X -- Zhou, Xuyu -- Johannes, Kellsey P -- Su, Maureen A -- Chang, Howard Y -- Krummel, Matthew F -- Anderson, Mark S -- K08 AI076429/AI/NIAID NIH HHS/ -- K08 AI076429-05/AI/NIAID NIH HHS/ -- P01 AI035297/AI/NIAID NIH HHS/ -- P01 AI035297-150009/AI/NIAID NIH HHS/ -- P01 AI035297-159001/AI/NIAID NIH HHS/ -- P01 AI035297-160009/AI/NIAID NIH HHS/ -- P01 AI035297-169001/AI/NIAID NIH HHS/ -- P01 AI035297-170009/AI/NIAID NIH HHS/ -- P01 AI035297-179001/AI/NIAID NIH HHS/ -- P30 DK063720/DK/NIDDK NIH HHS/ -- P30 DK063720-05/DK/NIDDK NIH HHS/ -- T32 GM007618/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Aug 8;321(5890):843-7. doi: 10.1126/science.1159407.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Diabetes Center, University of California San Francisco (UCSF), San Francisco, CA 94122, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18687966" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen Presentation ; Autoantigens/genetics/*immunology ; Autoimmunity ; Cell Proliferation ; Epithelial Cells/immunology ; Gene Expression Regulation ; Glucose-6-Phosphatase/immunology ; Lymph Nodes/cytology/*immunology/metabolism ; Lymphoid Tissue/*cytology/immunology/*metabolism ; Mice ; Mice, Transgenic ; Proteins/immunology ; *Self Tolerance ; Spleen/cytology/immunology/metabolism ; Stromal Cells/immunology/metabolism ; T-Lymphocytes/*immunology ; Thymus Gland/cytology/immunology ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    The Yin and Yang of T cell costimulation (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allison, J P -- Krummel, M F -- New York, N.Y. -- Science. 1995 Nov 10;270(5238):932-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7481795" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antigens, CD ; Antigens, CD28/*immunology ; Antigens, CD80/immunology ; Antigens, Differentiation/*immunology ; CTLA-4 Antigen ; Down-Regulation ; Humans ; *Immunoconjugates ; *Lymphocyte Activation ; Mice ; Mice, Knockout ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Enhancement of antitumor immunity by CTLA-4 blockade (1996)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1996-03-22
    Description: One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leach, D R -- Krummel, M F -- Allison, J P -- CA09179/CA/NCI NIH HHS/ -- CA40041/CA/NCI NIH HHS/ -- CA57986/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1996 Mar 22;271(5256):1734-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8596936" target="_blank"〉PubMed〈/a〉
    Keywords: Abatacept ; Animals ; Antibodies/immunology ; Antigens, CD ; Antigens, CD28/immunology ; Antigens, CD80/immunology ; Antigens, Differentiation/*immunology ; CTLA-4 Antigen ; Female ; Graft Rejection ; *Immunoconjugates ; Immunologic Memory ; *Lymphocyte Activation ; Mice ; Mice, Inbred A ; Mice, Inbred BALB C ; Neoplasm Transplantation ; Neoplasms, Experimental/*immunology ; T-Lymphocytes/*immunology ; Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    Visualizing dynamic microvillar search and stabilization during ligand detection by T cells (2017)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2017-05-12
    Description: During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot–enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.
    Keywords: Cell Biology, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Immunity as a continuum of archetypes (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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