Institution
Walter and Eliza Hall Institute of Medical Research
Nonprofit•Melbourne, Victoria, Australia•
About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.
Topics: Antigen, Immune system, Population, T cell, Plasmodium falciparum
Papers published on a yearly basis
Papers
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TL;DR: The discovery that a small number of peptides can elicit the disease in patients suggests that a similar approach may be successful in humans as well, and a detailed molecular understanding of the peptides driving the immune response in celiac disease is required.
Abstract: Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4(+ )T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat alpha-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from omega-gliadin (wheat) and C-hordein (barley) but not alpha-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.
424 citations
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TL;DR: BCL-XL–selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax, and demonstrate the translational utility of this toolkit of selective BCL-2 family inhibitors.
Abstract: The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2-selective inhibitor venetoclax (ABT-199/GDC-0199), which demonstrates robust activity in these cancers but spares platelets. Navitoclax has also been shown to enhance the efficacy of docetaxel in preclinical models of solid tumors, but clinical use of this combination has been limited by neutropenia. We used venetoclax and the BCL-XL-selective inhibitors A-1155463 and A-1331852 to assess the relative contributions of inhibiting BCL-2 or BCL-XL to the efficacy and toxicity of the navitoclax-docetaxel combination. Selective BCL-2 inhibition suppressed granulopoiesis in vitro and in vivo, potentially accounting for the exacerbated neutropenia observed when navitoclax was combined with docetaxel clinically. By contrast, selectively inhibiting BCL-XL did not suppress granulopoiesis but was highly efficacious in combination with docetaxel when tested against a range of solid tumors. Therefore, BCL-XL-selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax. These studies demonstrate the translational utility of this toolkit of selective BCL-2 family inhibitors and highlight their potential as improved cancer therapeutics.
423 citations
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TL;DR: An overview of gluten T-cell epitopes restricted by celiac disease associated HLA-DQ molecules is given and a comprehensive, new nomenclature is suggested.
Abstract: Celiac disease is caused by an abnormal intestinal T-cell response to gluten proteins of wheat, barley and rye. Over the last few years, a number of gluten T-cell epitopes restricted by celiac disease associated HLA-DQ molecules have been characterized. In this work, we give an overview of these epitopes and suggest a comprehensive, new nomenclature.
423 citations
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TL;DR: In aged as compared with young people T-cell immune responses tested by three different systems were significantly depressed and the mortality of very old people, who were hyporesponsive in tests for delayed hypersensitivity, was significantly greater over a two-year period.
422 citations
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TL;DR: Two important new tools are presented that have enabled us to characterize some of the functions of the apicoplast and mitochondrion, and which will be of use to the wider malaria research community in elucidating the localization of other P. falciparum proteins.
419 citations
Authors
Showing all 5041 results
Name | H-index | Papers | Citations |
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Martin White | 196 | 2038 | 232387 |
Stuart H. Orkin | 186 | 715 | 112182 |
Tien Yin Wong | 160 | 1880 | 131830 |
Mark J. Smyth | 153 | 713 | 88783 |
Anne B. Newman | 150 | 902 | 99255 |
James P. Allison | 137 | 483 | 83336 |
Scott W. Lowe | 134 | 396 | 89376 |
Rajkumar Buyya | 133 | 1066 | 95164 |
Peter Hall | 132 | 1640 | 85019 |
Ralph L. Brinster | 131 | 382 | 56455 |
Nico van Rooijen | 130 | 513 | 62623 |
David A. Hafler | 128 | 558 | 64314 |
Andreas Strasser | 128 | 509 | 66903 |
Marc Feldmann | 125 | 663 | 64916 |
Herman Waldmann | 118 | 586 | 49942 |