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BACKGROUNDAutoimmune diseases often have strong genetic associations with specific HLA-DR alleles. The synovial lesion in chronic inflammatory forms of arthritis shows marked upregulation of HLA-DR molecules, including in postinfectious Lyme arthritis (LA). However, the identity of HLA-DR-presented peptides, and therefore the reasons for these associations, has frequently remained elusive.METHODSUsing immunopeptidomics to detect HLA-DR-presented peptides from synovial tissue, we identified T cell epitopes from 3 extracellular matrix (ECM) proteins in patients with postinfectious LA, identified potential Borreliella burgdorferi-mimic (Bb-mimic) epitopes, and characterized T and B cell responses to these peptides or proteins.RESULTSOf 24 postinfectious LA patients, 58% had CD4+ T cell responses to at least 1 epitope of 3 ECM proteins, fibronectin-1, laminin B2, and/or collagen Vα1, and 17% of 52 such patients had antibody responses to at least 1 of these proteins. Patients with autoreactive T cell responses had significantly increased frequencies of HLA-DRB1*04 or -DRB1*1501 alleles and more prolonged arthritis. When tetramer reagents were loaded with ECM or corresponding Bb-mimic peptides, binding was only with the autoreactive T cells. A high percentage of ECM-autoreactive CD4+ T cells in synovial fluid were T-bet-expressing Th1 cells, a small percentage were RoRγt-expressing Th17 cells, and a minimal percentage were FoxP3-expressing Tregs.CONCLUSIONAutoreactive, proinflammatory CD4+ T cells and autoantibodies develop to ECM proteins in a subgroup of postinfectious LA patients who have specific HLA-DR alleles. Rather than the traditional molecular mimicry model, we propose that epitope spreading provides the best explanation for this example of infection-induced autoimmunity.FUNDINGSupported by National Institute of Allergy and Infectious Diseases R01-AI101175, R01-AI144365, and F32-AI125764; National Institute of Arthritis and Musculoskeletal and Skin Diseases K01-AR062098 and T32-AR007258; NIH grants P41-GM104603, R24-GM134210, S10-RR020946, S10-OD010724, S10-OD021651, and S10-OD021728; and the G. Harold and Leila Y. Mathers Foundation, the Eshe Fund, and the Lyme Disease and Arthritis Research Fund at Massachusetts General Hospital.

Objective: HLA‐DR–expressing fibroblast‐like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. FLS‐derived extracellular matrix (ECM) proteins, including fibronectin‐1 (FN1), contain immunogenic CD4+ T cell epitopes in patients with postinfectious Lyme arthritis (LA). However, the role of FLS in presentation of these T cell epitopes remains uncertain. Methods: Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFNγ), Borrelia burgdorferi, and/or B burgdorferi peptidoglycan (PG) were assessed for properties associated with antigen presentation. HLA‐DR–presented peptides from stimulated LA FLS were identified by immunopeptidomics analysis. OT‐II T cells were co‐cultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APCs). Results: FLS expressed HLA‐DR molecules within inflamed synovial tissue and tendons from patients with postinfectious LA in situ. Major histocompatibility complex (MHC) class II and co‐stimulatory molecules were expressed by FLS following in vitro stimulation with IFNγ and B burgdorferi and presented both foreign and self‐MHC‐II peptides, including an immunogenic T cell epitope derived from Lyme autoantigen FN1. Stimulated FLS induced proliferation of naive OT‐II CD4+ T cells that were dependent on OT‐II antigen and CD40. Stimulation with B burgdorferi PG enhanced FLS‐mediated T cell activation. Conclusion: MHC‐II+ FLS are inducible APCs that can induce CD4+ T cell activation in an antigen‐ and CD40‐dependent manner. Activated FLS can also present ECM‐derived Lyme autoantigens, implicating FLS in amplifying tissue‐localized autoimmunity in LA. [ABSTRACT FROM AUTHOR]

Background During infection with the Lyme arthritis (LA) pathogen Borrelia burgdorferi , T-cell responses to both host and pathogen are dysregulated, resulting in chronic infection and frequent development of autoimmunity. Methods To assess CD4+ T-cell epitopes presented during development of LA, we used an unbiased, immunopeptidomics approach to characterize the major histocompatibility complex (MHC) class II immunopeptidome in B burgdorferi -infected C57BL/6 (B6) mice, which develop mild, self-limiting LA, and infected B6 Il10 −/− mice, which develop severe, persistent LA at 0, 4, and 16 weeks postinfection (22–23 mice per group). Results Peptides derived from proteins involved in adaptive T- and B-cell responses and cholesterol metabolism, including human Lyme autoantigen apolipoprotein B-100 (apoB-100), were enriched in infected Il10−/− mice; whereas peptides derived from proteins involved in neutrophil extracellular net formation were enriched in infected B6 mice. Presentation of apoB-100 peptides showed evidence of epitope expansion during infection. Of several identified B burgdorferi peptides, only 1, a methyl-accepting chemotaxis protein peptide Mcp4442–462, was immunogenic. Conclusions ApoB-100, a human Lyme autoantigen, undergoes marked epitope expansion during LA development. The paucity of immunogenic B burgdorferi epitopes supports previous findings suggesting CD4+ T-cell responses are suppressed in murine LA. [ABSTRACT FROM AUTHOR]

Th e Republic of Moldova is considering the adoption of trial by jury in select criminal cases. Th e following article is intended to contribute to the discussion of that proposal. Th e article will briefl y describe the history of juries under the English common law and as adopted by the United States. It will then outline some of the basic procedures in trials by jury as currently practiced in the United States federal court system.

The effect of uniaxial drawing of biodegradable soy protein isolate (SPI) polymer film on mechanical properties was investigated to accelerate the efforts to develop SPI films with improved properties. The films containing 0-30 wt% glycerol were drawn uniaxially up to a draw ratio of 2.5. The mechanical properties of the SPI film increased significantly after uniaxial drawing. The tensile strength of the undrawn film (49.7 MPa) was approximately doubled by subjecting the film to uniaxial drawing to a D.R. of 2.5. Wide-angle X-ray diffraction and differential scanning calorimetry measurements did not show evidence of generation of a crystal phase in the drawn SPI films. ATR-FTIR revealed that the protein film contained mainly α-helix and β-sheets secondary structures. Microwave molecular orientation analysis showed that birefringence increased with increasing draw ratios. Mechanical anisotropy of the SPI film via orientation of α-helix and β-sheets structure is thought to be responsible for the enhancement of mechanical properties with uniaxial drawing of the SPI films. POLYM. ENG. SCI., 47:374-380, 2007. © 2007 Society of Plastics Engineers, INTRODUCTION Recently, soy protein has been considered as an alternative to synthetic polymers derived from petroleum resources in the manufacture of plastics and adhesives. This is because plastics made from [...]