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Suboptimal stimulation by weak agonist epitope variants does not drive dysfunction of HIV-1-specific CTL clones

Mark A. Grossman, Christian Hofmann, Hwee L. Ng, Otto O. Yang
2019 AIDS (London)  
To assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8 T lymphocyte (CTL) clones as a mechanism of dysfunction.  ...  variants 1 and 2 functioned as APL with successively reduced CTL triggering.  ...  The indicated relative levels of transcripts for proteins associated with activation/metabolism (black labels), exhaustion (red labels), apoptosis (green labels), and anergy (blue labels) reflect average  ... 
doi:10.1097/qad.0000000000002259 pmid:31306165 pmcid:PMC7046083 fatcat:qdvwbnoa6bat7ganeizkilkihy

Educational Case: Acute Promyelocytic Leukemia With PML-RARA

Rebecca L. Kunak, Amyn Rojiani, Natasha M. Savage
2019 Academic Pathology  
These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.  ...  For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 .  ...  Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.  ... 
doi:10.1177/2374289519875647 pmid:31555723 pmcid:PMC6753509 fatcat:bshbjyhlybftjmq4gw6xly23ae

Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia

Z Chen, N J Brand, A Chen, S J Chen, J H Tong, Z Y Wang, S Waxman, A Zelent
1993 EMBO Journal  
Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL, further implicating the RAR alpha in leukaemogenesis and also suggesting  ...  Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues.  ...  Variant translocations have also been reported in APL (Mitelman, 1991) . These translocations often involve chromosomes 15, 17 and a third chromosome.  ... 
pmid:8384553 pmcid:PMC413318 fatcat:6ujkuv7iozgjfi7f2pyj6dsp4a

Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation

L. K. McNeil, B. D. Evavold
2002 Proceedings of the National Academy of Sciences of the United States of America  
MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists  ...  Thus, receptor reserve dissociates peripheral T cell response and thymocyte negative selection to MHC variants supporting a spare receptor model for TCR interaction with ligand.  ...  Jensen, and members of the Evavold laboratory for critical reading of the manuscript. This work was supported by American Cancer Society Grant RPG-00-314.  ... 
doi:10.1073/pnas.072673899 pmid:11904393 pmcid:PMC123680 fatcat:osftojrhi5huvhc4rcaezvvqjq

Mutations in Complement Regulatory Proteins Predispose to Preeclampsia: A Genetic Analysis of the PROMISSE Cohort

Jane E. Salmon, Cara Heuser, Michael Triebwasser, M. Kathryn Liszewski, David Kavanagh, Lubka Roumenina, D. Ware Branch, Tim Goodship, Veronique Fremeaux-Bacchi, John P. Atkinson, Nicholas M. Fisk
2011 PLoS Medicine  
Conclusion: The presence of risk variants in complement regulatory proteins in patients with SLE and/or APL Ab who develop preeclampsia, as well as in preeclampsia patients lacking autoimmune disease,  ...  Pregnancy in women with systemic lupus erythematosus (SLE) or antiphospholipid antibodies (APL Ab)autoimmune conditions characterized by complement-mediated injury-is associated with increased risk of  ...  Jill Buyon, Ware Branch, Flint Porter, Allen Sawitzke, Michael Lockshin, Michelle Petri, Carl Laskin, Lisa Sammaritano, Joan Merrill, and Mary Stephenson) for recruiting study patients and Dr.  ... 
doi:10.1371/journal.pmed.1001013 pmid:21445332 pmcid:PMC3062534 fatcat:2sefhgnknzfcpizgbnnujki4xi

Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis

Dag Leonard, Elisabet Svenungsson, Johanna Dahlqvist, Andrei Alexsson, Lisbeth Ärlestig, Kimberly E Taylor, Johanna K Sandling, Christine Bengtsson, Martina Frodlund, Andreas Jönsen, Susanna Eketjäll, Kerstin Jensen-Urstad (+8 others)
2018 Annals of the Rheumatic Diseases  
investigated possible functional effects of associated gene variants.  ...  ExtEndEd rEport Novel gene variants associated with cardiovascular disease in systemic lupus erythematosus and rheumatoid arthritis dag Leonard, 1 Elisabet Svenungsson, 2 Johanna dahlqvist, 3 Andrei  ... 
doi:10.1136/annrheumdis-2017-212614 pmid:29514802 pmcid:PMC6029634 fatcat:cdskzmg3fvdadowz5brcz6c2li

Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia

Jeff L Hummel, Richard A Wells, Ian D Dubé, Jonathan D Licht, Suzanne Kamel-Reid
1999 Oncogene  
A small number of variant APL translocations have also been shown to involve rearrangements that fuse RARa to partner genes other than PML, namely PLZF, NPM, and NuMA.  ...  We describe the molecular characterization of a t(5;17)(q35;q21) variant translocation involving the NPM gene, identi®ed in a pediatric case of APL.  ...  Acknowledgements We are indebted to M Freedman, W Vanek and T Grunberger (Hospital for Sick Children, Toronto, Canada) for providing patient material for our studies and for help with the interpretation  ... 
doi:10.1038/sj.onc.1202357 pmid:9989813 fatcat:po3dtatffzhs7ip2dt65ihgdri

Apolipoprotein H Promoter Polymorphisms in Relation to Lupus and Lupus-related Phenotypes

S. SURESH, F. Y. K. DEMIRCI, E. JACOBS, A. H. KAO, E. Y. RHEW, D. K. SANGHERA, F. SELZER, K. SUTTON-TYRRELL, D. McPHERSON, F. A. BONTEMPO, C. M. KAMMERER, R. RAMSEY-GOLDMAN (+2 others)
2009 Journal of Rheumatology  
We tested the hypothesis that common promoter variation in the APOH gene (encoding for ss(2)-glycoprotein I) is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes  ...  Our data indicate that APOH promoter variants may be involved in the etiology of SLE, especially the risk for autoimmune-mediated cardiovascular disease.  ...  ACKNOWLEDGMENT We thank Bonnie Kane, BS, and Beverly Smulevitz, BS, for their technical assistance.  ... 
doi:10.3899/jrheum.080482 pmid:19132787 pmcid:PMC2667221 fatcat:5sc3iyv7bfeffdxxpdh2kvw4qa

Stimulation of Naive CD8 + T Cells by a Variant Viral Epitope Induces Activation and Enhanced Apoptosis

Rebecca M. Ream, Jie Sun, Thomas J. Braciale
2010 Journal of Immunology  
Acknowledgments We thank the members of the Braciale Lab for critical comments and B. Small and T. Gill for technical assistance. Disclosures The authors have no financial conflicts of interest.  ...  As observed for variant peptides that serve as APLs, activated/effector CL-4 had a lower functional avidity for the variant epitope than for the agonist epitope.  ...  (27) , this difference may stem from a relatively low functional avidity of the CL-4 TCR for the variant Japan HA epitope than for the APL used in the OT-1 TCR Tg model.  ... 
doi:10.4049/jimmunol.0902448 pmid:20139280 pmcid:PMC2996134 fatcat:v53vristr5hthbgzojs6jcnzpe

The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway

Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
2016 Cell Death and Differentiation  
We constructed a human APL-ascites SCID mouse model to validate the function of HOTAIRM1 and its regulatory pathway in vivo.  ...  However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis.  ...  Author contributions Z-HC designed and performed the research, analyzed the data and wrote the manuscript. W-TW, WH, KF, Y-MS and S-RL performed the research and analyzed the data.  ... 
doi:10.1038/cdd.2016.111 pmid:27740626 pmcid:PMC5299705 fatcat:qt2gzmexgzavpk6s7mxdrnteui

Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands

Y. Ghendler, M.-k. Teng, J.-h. Liu, T. Witte, J. Liu, K. S. Kim, P. Kern, H.-C. Chang, J.-h. Wang, E. L. Reinherz
1998 Proceedings of the National Academy of Sciences of the United States of America  
V4L (L4) inducing phenotypic and functional T cell maturation.  ...  Using TCR-transgenic (N15tg) ␤ 2microglobulin-deficient (␤ 2 m ؊/؊ ) RAG-2 ؊/؊ H-2 b mice specific for the VSV8 (RGYVYQGL) octapeptide bound to K b , we identified a single weak agonist peptide variant  ...  .), and AI39098 (to H.-C.C.). P.K. was supported by fellowships from the Schweizerischer Nationalfond and Schweizerische Krebsliga. We thank Drs. J. Griffin and L.  ... 
doi:10.1073/pnas.95.17.10061 pmid:9707600 pmcid:PMC21461 fatcat:sjb6s2fmxvczznyppvcdhwz6t4

Naturally occurring CD4+ T-cell epitope variants act as altered peptide ligands leading to impaired helper T-cell responses in hepatitis C virus infection

Matthew F. Cusick, Meiying Yang, Joan C. Gill, David D. Eckels
2011 Human Immunology  
In the current study, we hypothesize that viral variants are acting as altered peptide ligands (APLs).  ...  In addition, MHC class II tetramer staining demonstrated that variant peptide-MHC complexes were able to specifically bind to NS3 358-375 T-cell clones and that both the variant and NS3 358-375 tetramers  ...  The authors thank Drs Matthew Williams, Robert Fujinami, Curt Hagedorn, and Matthew Mulvey for helpful discussions along with Jane Libbey for critical feedback of this manuscript.  ... 
doi:10.1016/j.humimm.2011.02.010 pmid:21377503 pmcid:PMC3086659 fatcat:dtdu6o7jkngujaztlg7y3bcmeq

Discovery of APL-1030, a Novel, High-Affinity Nanofitin Inhibitor of C3-Mediated Complement Activation

Joshua Garlich, Mathieu Cinier, Anne Chevrel, Anaëlle Perrocheau, David J. Eyerman, Mark Orme, Olivier Kitten, Lukas Scheibler
2022 Biomolecules  
C3b-binding sites of APL-1030 and compstatin were shown to overlap by X-ray crystallography of C3b-bound APL-1030.  ...  APL-1030 is thermostable, binds C3 (KD, 1.59 nM) and C3b (KD, 1.11 nM), and inhibits complement activation via classical (IC50 = 110.8 nM) and alternative (IC50 = 291.3 nM) pathways in Wieslab assays.  ...  , and Andre White.  ... 
doi:10.3390/biom12030432 pmid:35327625 pmcid:PMC8946527 fatcat:7lg5vwbn2ve7znrxuaw3y3534m

Acute promyelocyte leukemia arose from CALR 1 mutated post essential thrombocythemia- myelofibrosis with splanchnic vein thrombosis: a case report

Morsia E, Goteri G, Torre E, Garvey KB, Discepoli G, Tassoni A, Mancini S, Giantomassi F, Poloni A, Olivieri A, Rupoli S
2021 Leukemia Research Reports  
Leukemic transformation rates at 20 years are estimated at less than 5% for ET and risk factors for leukemic transformation are advanced age, thrombosis history, leukocytosis, and anemia.  ...  Calreticulin (CALR) mutation type 1 frequencies in ET are estimated between 7% and 11% and ET patients carrying CALR type 1 mutation are associated with lower risk of thrombosis but higher risk of myelofibrosis  ...  Acknowledgements The authors would like to acknowledge the patient, and the staff involved in his care.  ... 
doi:10.1016/j.lrr.2021.100243 pmid:34040959 pmcid:PMC8142272 fatcat:7sxm6whbezbuhgmhnza5nh2mn4

Aberrant Corepressor Interactions Implicated in PML-RARα and PLZF-RARα Leukemogenesis Reflect an Altered Recruitment and Release of Specific NCoR and SMRT Splice Variants

Brenda J. Mengeling, Theresa Q. Phan, Michael L. Goodson, Martin L. Privalsky
2010 Journal of Biological Chemistry  
The positions of the RAR␣, PML-RAR␣, or PLZF-RAR␣ homodimers (labeled RR, PP, or ZZ, respectively) and RXR␣ heteromers (labeled RX, PX, and ZX, respectively) in the absence of corepressor are indicated  ...  All of the reactions contained a fixed amount of 32 P-labeled probe and each RAR␣ or x-RAR␣ protein; RXR␣ and/or NCoR was included or omitted as indicated.  ...  Acknowledgments-We thank Scott Kogan for the generous gift of mouse PML-RAR␣ APL cells, Joost Martens and Henk Stunnenberg for the generous gift of PR9 cells, and Liming Liu for superb technical assistance  ... 
doi:10.1074/jbc.m110.200964 pmid:21131350 pmcid:PMC3039402 fatcat:kefuhp5injbzbmn7ywp7ysk3pa
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