La Jolla Institute for Allergy & Immunology is a non-profit biomedical research institution founded in 1988 and located in La Jolla, California. The Institute's main focus is understanding the immune response to infectious agents and cancers and on advancing progress toward the prevention, treatment, and cure of immune system diseases. Wikipedia.
La Jolla Institute for Allergy and Immunology | Date: 2016-05-10
A composition comprising a TRAIL-R2 receptor or fragment thereof bound to a ligand in crystalline form is presently provided along with novel binding sites and binding agents of a TRAIL receptor. Also provided are methods of designing a compound, protein or peptide and identifying a binding agent that interacts with a TRAIL receptor. The present invention further provides methods of modulating binding of a TRAIL receptor to a ligand, the methods comprising contacting the TRAIL receptor with a binding agent, ligand, or an agonist or antagonist thereof, that interacts with a novel binding site described herein.
La Jolla Institute for Allergy and Immunology | Date: 2015-04-09
The invention relates to novel targets for immune response modulation, treatment of tuberculosis infection and epitopes of Mycobacterium tuberculosis, or subsequences, portions or modifications thereof, and methods and compounds for treatment and prevention of tuberculosis infection.
La Jolla Institute for Allergy and Immunology | Date: 2016-10-14
Methods of treating inflammatory conditions, disease and disorders are provided. Method include, for example, contacting or administering a sufficient amount of a LIGHT inhibitor to a subject to treat the inflammatory condition, disease or disorder.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-22-2016 | Award Amount: 12.56M | Year: 2016
The ZikaPLAN initiative combines the strengths of 25 partners in Latin America, North America, Africa, Asia, and various centres in Europe to address the urgent research gaps (WP 1-8) in Zika, identifying short-and long term solutions (WP 9-10) and building a sustainable Latin-American EID Preparedness and Response capacity (WP 11-12). We will conduct clinical studies to further refine the full spectrum and risk factors of congenital Zika syndrome (including neurodevelopmental milestones in the first 3 years of life), and delineate neurological complications associated with Zika due to direct neuroinvasion and immune-mediated responses. Laboratory based research to unravel neurotropism, investigate the role of sexual transmission, determinants of severe disease, and viral fitness will envelop the clinical studies. Burden of disease and modelling studies will assemble a wealth of data including a longitudinal cohort study of 17,000 subjects aged 2-59 in 14 different geographic locations in Brazil over 3 years. Data driven vector control and vaccine modelling as well as risk assessments on geographic spread of Zika will form the foundation for evidence-informed policies. The Platform for Diagnostics Innovation and Evaluation will develop novel ZIKV diagnostic tests in accordance with WHO Target Product Profiles. Our global network of laboratory and clinical sites with well-characterized specimens is set out to accelerate the evaluation of the performance of such tests. Based on qualitative research, we will develop supportive, actionable messages to affected communities, and develop novel personal protective measures. Our final objective is for the Zika outbreak response effort to grow into a sustainable Latin-American network for emerging infectious diseases research preparedness. To this end we will engage in capacity building in laboratory and clinical research, collaborate with existing networks to share knowledge and tackle regulatory and other bottlenecks.
Bottini N.,La Jolla Institute for Allergy and Immunology |
Peterson E.J.,University of Minnesota
Annual Review of Immunology | Year: 2014
Inheritance of a coding variant of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene is associated with increased susceptibility to autoimmunity and infection. Efforts to elucidate the mechanisms by which the PTPN22-C1858T variant modulates disease risk revealed that PTPN22 performs a signaling function in multiple biochemical pathways and cell types. Capable of both enzymatic activity and adaptor functions, PTPN22 modulates signaling through antigen and innate immune receptors. PTPN22 plays roles in lymphocyte development and activation, establishment of tolerance, and innate immune cell-mediated host defense and immunoregulation. The disease-Associated PTPN22-R620W variant protein is likely involved in multiple stages of the pathogenesis of autoimmunity. Establishment of a tolerant B cell repertoire is disrupted by PTPN22-R620W action during immature B cell selection, and PTPN22-R620W alters mature T cell responsiveness. However, after autoimmune attack has initiated tissue injury, PTPN22-R620W may foster inflammation through modulating the balance of myeloid cell-produced cytokines. © 2014 by Annual Reviews. All rights reserved.
Stanford S.M.,La Jolla Institute for Allergy and Immunology
Nature Reviews Rheumatology | Year: 2014
PTPN22 encodes a tyrosine phosphatase that is expressed by haematopoietic cells and functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signalling and by selectively promoting type I interferon responses after activation of myeloid-cell pattern-recognition receptors. A single nucleotide polymorphism of PTPN22, 1858C>T (rs2476601), disrupts an interaction motif in the protein, and is the most important non-HLA genetic risk factor for rheumatoid arthritis and the second most important for juvenile idiopathic arthritis. PTPN22 exemplifies a shared autoimmunity gene, affecting the pathogenesis of systemic lupus erythematosus, vasculitis and other autoimmune diseases. In this Review, we explore the role of PTPN22 in autoimmune connective tissue disease, with particular emphasis on candidate-gene and genome-wide association studies and clinical variability of disease. We also propose a number of PTPN22-dependent functional models of the pathogenesis of autoimmune diseases.
Croft M.,La Jolla Institute for Allergy and Immunology
Seminars in Immunology | Year: 2014
Proteins in the TNF/TNFR superfamily are recognized as major regulators of the activity of conventional CD4 and CD8 T cells, and also of regulatory T cells (Treg). Stimulatory molecules such as OX40, CD27, GITR, DR3, CD30, 4-1BB, TACI, and TNFR2 can promote division and survival in T cells, enhance effector activity including cytokine production, and drive the generation of T cell memory. They also display the capacity to block the development of inducible Treg cells or inhibit suppressive activity in Treg cells. Additionally, molecules such as Fas, TNFR1, and TRAILR promote apoptotic death in T cells and generally limit T cell activity. Although our knowledge of these proteins is quite good at this point in time, there are still many unknowns regarding their function, their expression patterns, and the involvement of these different molecules at various stages of the T cell response that occurs in autoimmunity, cancer, infectious disease, and during vaccination. Importantly, it is still unresolved how similar or dissimilar each of these receptors are to one another, the extent to which cooperation occurs between family members, and whether alternate TNF-TNFR interactions induce qualitatively different cellular responses. All of the molecules are attractive targets for immunotherapy of human disease, but it is not yet clear how to differentiate between them and make an informed decision as to whether any one protein may be the preferred focus of clinical development for a given specific disease indication. This review will highlight unanswered questions related to these molecules and the biology of T cells, and describe possible future directions for research in this area. Expanding our knowledge of how the TNF/TNFR family control T cells will undoubtedly help fulfill the promise of these molecules for providing efficacious clinical therapy of immune system disease. © 2014 Elsevier Ltd.
Croft M.,La Jolla Institute for Allergy and Immunology
Annual Review of Immunology | Year: 2010
TNFR/TNF superfamily members can control diverse aspects of immune function. Research over the past 10 years has shown that one of the most important and prominent interactions in this family is that between OX40 (CD134) and its partner OX40L (CD252). These molecules strongly regulate conventional CD4 and CD8 T cells, and more recent data are highlighting their ability to modulate NKT cell and NK cell function as well as to mediate cross-talk with professional antigen-presenting cells and diverse cell types such as mast cells, smooth muscle cells, and endothelial cells. Additionally, OX40-OX40L interactions alter the differentiation and activity of regulatory T cells. Blocking OX40L has produced strong therapeutic effects in multiple animal models of autoimmune and inflammatory disease, and, in line with a prospective clinical future, reagents that stimulate OX40 signaling are showing promise as adjuvants for vaccination as well as for treatment of cancer. Copyright © 2010 by Annual Reviews. All rights reserved.
Crotty S.,La Jolla Institute for Allergy and Immunology
Immunological Reviews | Year: 2012
T-cell help to B cells is a fundamental aspect of adaptive immunity and the generation of B-cell memory (memory B cells and plasma cells). Follicular helper CD4 + T (Tfh) cells are the specialized providers of B-cell help, and Tfh cells depend on Bcl6 for their differentiation. This review discusses Tfh cell functions, transcription factors, and induction signals, with particular focus on the richness of the underlying biology and assessing the simplicity or complexity of each of these processes. © 2012 John Wiley & Sons A/S.
Crotty S.,La Jolla Institute for Allergy and Immunology
Immunity | Year: 2014
Follicular helper T (Tfh) cells are specialized providers of Tcell help to B cells, and are essential for germinal center formation, affinity maturation, and the development of most high-affinity antibodies and memory B cells. Tfh cell differentiation is a multistage, multifactorial process involving B cell lymphoma 6 (Bcl6) and other transcription factors. This article reviews understanding of Tfh cell biology, including their differentiation, migration, transcriptional regulation, and B cell help functions. Tfh cells are critical components of many protective immune responses against pathogens. As such, there is strong interest in harnessing Tfh cells to improve vaccination strategies. Tfh cells also have roles in a range of other diseases, particularly autoimmune diseases. Overall, there have been dramatic advances in this young field, but there is much to be learned about Tfh cell biology in the interest of applying that knowledge to biomedical needs. © 2014 Elsevier Inc.