Immunology and Diabetes - Human Immunology headed by Dr Stuart Mannering
Human Immunology headed by Dr Stuart Mannering
Research Overview
The goal of the Human T-cell Immunology Lab, within the Immunology of Diabetes Unit, is twofold. First, to understand why the insulin-producing cells are attacked by the immune system’s T cells and second, to use this information to develop new assays to measure these autoimmune responses and ways to stop them developing. Our research focuses on human CD4+ T cells because they play a pivotal role in the control of the (auto)immune response.
In 2005, we published the first report of an immune response directed against and modified form of insulin. The idea that autoimmune responses are directed against parts of self tissue that are modified for some reason has been around for a long time, but it has been very difficult to prove whether this applies to human T1D. Since then our work has focused on developing improved methods to analyze human, antigen-specific, T-cell function and using human T-cell clones to examine the specificity of autoimmune T cell responses in T1D.
Research Themes
Blunting the autoimmune response toward human islets in type 1 diabetes: A mouse model of the human
Identification of islet antigens recognized by CD4+ T cells in human type 1 diabetes
Autoimmune and allo-immune responses following islet transplantation
Staff
Dr Stuart Mannering
Andra Necula
Janine Kuelich
Tara Catterall
Publication Highlights
Mannering SI, Pang SH, Williamson NA, Naselli G, Reynolds EC, O'Brien-Simpson NM, Purcell AW, Harrison LC, The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes. Clinical and experimental immunology 2009; 156: 226-31.
Campbell PD, Estella E, Dudek NL, Jhala G, Thomas HE, Kay TW, Mannering SI. Cytotoxic T-lymphocyte-mediated killing of human pancreatic islet cells in vitro. Human Immunology 2008; 69: 543-551
Dudek NL, Maier S, Chen ZJ, Mudd PA, Mannering SI, Jackson DC, Zeng W, Keech CL, Hamlin K, Pan ZJ, Davis-Schwarz K, Workman-Azbill J, Bachmann M, McCluskey J, Farris AD. T cell epitopes of the La/SSB autoantigen in humanized transgenic mice expressing the HLA class II haplotype DRB1*0301/DQB1*0201. Arthritis & Rheumatism 2007; 56:3387-98
Henderson KN, Tye-Din JA, Reid HH, Chen Z, Borg NA, Beissbarth T, Tatham A, Mannering SI, Purcell AW, Dudek NL, van Heel DA, McCluskey J, Rossjohn J, Anderson RP. A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease. Immunity 2007; 27:23-34
Mannering SI, Harrison LC, Williamson NA, Morris JS, Thearle DJ, Jensen KP, Kay TW, Rossjohn J, Falk BA, Nepom GT, Purcell AW. The insulin A-chain epitope recognized by human T cells is posttranslationally modified. Journal of Experimental Medicine 2005; 202: 1191-7
Mannering SI, Dromey JA, Morris JS, Thearle DJ, Jensen KP, Harrison LC. An efficient method for cloning human autoantigen-specific T cells. Journal of Immunological Methods 2005; 298:83-92
Mannering SI, Morris JS, Stone NL, Jensen KP, van Endert PM, Harrison LC. CD4+ T Cell Proliferation in Response to GAD and Proinsulin in Healthy, Pre-diabetic, and Diabetic Donors. Annals of the New York Academy of Sciences 2004; 1037:16-21
Mannering SI, Morris JS, Jensen KP, Purcell AW, Honeyman MC, van Endert PM, Harrison LC. A sensitive method for detecting proliferation of rare autoantigen-specific human T cells. Journal of Immunological Methods 2003; 283:173-83