p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
(2011) Alekseev et al. Reproductive Biology and Endocrinology. Background: NASP (Nuclear Autoantigenic Sperm Protein) is a histone chaperone that is present in all dividing cells. NASP has two splice variants: tNASP and sNASP. Only cancer, germ, transformed, and embryonic cells have a high level ...
Identification of novel autoantigens via mass spectroscopy-based antibody-mediated identification of autoantigens (MS-AMIDA) using immune thrombocytopenic purpura (ITP) as a model ...
Schwartz, M; Sela, B A.; and Eshhar, N, "Antibodies to gangliosides and myelin autoantigens are produced in mice following sciatic nerve injury." (1982). Subject Strain Bibliography 1982. 2752 ...
Several scleroderma autoantigens are uniquely fragmented by Fe/ascorbate or Cu/H2O2 oxidation reactions. HeLa lysates were prepared as described in the Materi
The findings here demonstrate that selectively restoring B7.2 expression on otherwise self-tolerant B cells is sufficient to switch their fate from peripheral deletion to large-scale proliferation and autoantibody secretion during interactions with specific CD4+ T cells. Of the many early signals and responses to BCR engagement that are repressed or altered in tolerant B cells ((12)-(14)), the data here single out repression of the B7.2 response as being necessary to allow peripheral tolerance by FasL/Fas-mediated clonal abortion. The findings raise interesting questions about how B7.2 switches the outcome of interactions between tolerant B and T cells, and highlight the regulation of B7.2 in B cells as a key process that may be dysregulated by inherited or acquired triggers to systemic autoimmune disease.. Three possible mechanisms may in principle explain how dysregulated expression of B7.2 on tolerant B cells switches the outcome of interactions with autoantigen-specific T cells from deletion ...
PURPOSE: The therapeutic importance of immune responses against single versus multiple antigens is poorly understood. There also remains insufficient understanding whether responses to one subset of antigens are more significant than another. Autoantibodies are frequent in cancer patients. They can pose no biological significance or lead to debilitating paraneoplastic syndromes. Autoreactivity has been associated with clinical benefits, but the magnitude necessary for meaningful results is unknown. Autologous tumor cells engineered to secrete granulocyte macrophage colony-stimulating factor generate immune infiltrates in preexisting metastases with associated tumor destruction. We sought to identify targets of responses from this vaccination strategy. EXPERIMENTAL DESIGN: Postvaccination sera used in screening a cDNA expression library prepared from a densely infiltrated metastasis of a long-term surviving melanoma patient identified several autoantigens. Additional autoantigens were identified through
Most autoreactive T cells are exposed to self-antigen either in the thymus or the periphery, and high avidity T cells are eliminated in both compartments. In contrast, lower avidity T cells are often found in ongoing autoimmune diseases (Bulek et al., 2012) and in anti-tumor responses (McMahan and Slansky, 2007). Thus, expression of a low avidity TCR, allowing autoreactive T cells to bypass elimination, is a major mechanism by which autoreactive T cells escape tolerance (von Herrath et al., 1994; Nugent et al., 2000; Zehn and Bevan, 2006). However, up to this point, we had limited insight into the phenotypic and functional characteristics of these low avidity self-reactive T cells. Thus, it was unclear how self-antigen recognition in the thymus or periphery impacts the function of these T cells and whether such exposure imprinted mechanisms that restrict their activation. The failure to negatively select low avidity self-reactive T cells stimulated us to study how well these T cells respond to ...
Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major h
Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen.: The Ku complex, a heterodimer of 86- and 70-kD proteins, is a nuclear
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire against self-antigens is likely to be more relevant than the potential reactivity of naive T cells. Methods to eliminate such an established T-cell response are less well understood. In this study, we explored the effectiveness of intravenous soluble antigen to eliminate a pre-existing T-cell response against αB-crystallin, a candidate autoantigen in MS. We used mice that are deficient for the target antigen. This condition allowed for a vigourous T-cell and antibody response to develop upon immunization, and eliminated all possible endogenous mechanisms of tolerance for αB-crystallin that are found in normal rodents. When applied 3 weeks after priming ...
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Clearly, several factors can contribute to the clinical manifestations of EAE in any one particular model, perhaps the two greatest contributors being the genetic background and the immunizing myelin antigen or the target autoantigen. It has been reported that the antigenic epitope specificity of myelin antigens influences the phenotype of EAE and location of the lesions. In Balb/c (IAd, IEd) mice, IAd-restricted MBP 59-76-specific T cells induce classical EAE with characteristic inflammation and demyelination of the CNS (34). In contrast, IEd-restricted MBP 151-168-specific T cells induce inflammation and demyelination of preferentially PNS myelin including nerves in the hind leg and spinal roots. The authors suggested two possibilities to explain their result. The first is that the distinct inflammation sites may be attributable to qualitative differences in MBP isoform composition in the CNS and PNS. The MBP 151-168 epitope, which is encoded by exons 6 and 7, exists only in the 18.5- and ...
The presence of autoreactive T-cell clones in the T-cell repertoire is determined in the thymus, but activation and expansion of naïve clonal populations is regulated in the periphery by antigen encounter, homeostatic mechanisms, and the inhibitory network of Tregs. Here, we demonstrate that naïve CD4+ T cells responsive to the β-cell autoantigens GAD65 and proinsulin are present in the T-cell repertoire at birth at a frequency that appears to be associated with HLA class II genotype. Neonatal naïve T cells were highly sensitive to IL-7, but antigen presentation was inefficient at birth and rescued by 8 months of age. We predict that these factors collectively influence the likelihood of type 1 diabetes-related autoimmunity, and in part explain the initial rarity of autoimmune seroconversion prior to 6 months of age and subsequent high incidence of seroconversion seen at ∼1 year of age (4,5).. Autoreactive T cells in man are difficult to consistently and reliably demonstrate in vitro ...
May be involved in protein transport from Golgi to cell surface. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS (By similarity).
Goat polyclonal antibody raised against synthetic peptide of GOLGA3. A synthetic peptide corresponding to human GOLGA3. (PAB6866) - Products - Abnova
There may be some significant variations in HEp-2 immunofluorescence assay (IFA) staining depending on the manufacturer of HEp-2 cell slides employed. Some autoantigens and epitopes may not be available in some cell preparations. To ensure that the HEp-2 slide in use can detect anti-Ro60/SS-A and anti-La/SS-B staining, appropriate reference materials, such as those from www.AutoAb.org, should be used to verify the HEp-2 slide and other reagents employed in the assay. Experts in the field also advise to have low titer positive controls to test each new batch of HEp-2 slides for appropriate sensitivity. If well-defined standards for anti-Ro60/SSA and anti-La/SS-B do not show nuclear staining, this is a clear indication that the IFA has not been optimized for those autoantigens. The Ro60 autoantigen, in particular, seems to be labile and can be extracted by mild solvents and even prolonged exposure to some buffers. Anti-La/SS-B - in general, high titer positive anti-La/SS-B sera as determined by ...
Background: A 20-year longitudinal study of over 12,000 women shows a higher epidemiologic risk for OvCa and other cancers among women with infertility (Brinton et al, 2005, Epidemiology). In recent studies of an autoimmune etiology for some women with infertility we identified ovarian autoantigens. Several of the autoantigens were also reported as autoantigens in OvCa. Therefore the objective was to determine if there are commonly occurring autoantibodies in sera of women with infertility and OvCa in order to identify a potential risk group that would benefit from closer monitoring and earlier detection of OvCa.. Methods: We assessed antibodies to eight recombinant proteins previously identified as OvCa markers or as autoantigens in infertility. Sera (1:100) from women with infertility (n=28), malignant OvCa (n=21), benign ovarian tumors (n=9) and healthy control women without cancer (n=6) were assessed against the antigens (50 ng/well) in standard immunoassays. The antigens included ...
Complete information for SPA17 gene (Protein Coding), Sperm Autoantigenic Protein 17, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for GOLGA6A gene (Protein Coding), Golgin A6 Family Member A, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
GOLGA2/GM130 antibody Rabbit Polyclonal from Proteintech validated in Western Blot (WB), Immunohistochemistry (IHC), Immunofluorescence (IF), Flow Cytometry (FC), Enzyme-linked Immunosorbent Assay (ELISA) applications. This antibody reacts with human, dog samples. Cat.No. 11308-1-AP.
Intracellular Redistribution of Truncated La Protein Produced by Poliovirus 3Cpro-Mediated Cleavage: The La autoantigen (also known as SS-B), a cellular RNA bin
90. Thymic expression of autoantigens correlates with resistance to autoimmune disease. Journal of Pain and Symptom Management, 20(4), 253в258. D.
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Looking for online definition of GOLGA6L2 in the Medical Dictionary? GOLGA6L2 explanation free. What is GOLGA6L2? Meaning of GOLGA6L2 medical term. What does GOLGA6L2 mean?
Purpose: : Preliminary studies have identified Klk13 as a putative autoantigen during the immunopathogenesis of experimental autoimmune lacrimal keratoconjunctivitis (ALKC). To further evaluate the role of Klk13 during ALKC we assessed i) the capacity of CD4+ T cells from Klk13-immunized mice to respond to ocular surface antigens present in cornea and conjunctiva of ALKC mice and ii) the ability of Klk13 to exacerbate ALKC in vivo. Methods: : A co-culture experiment was performed to determine if immunization with Klk13 potentiates the proliferative response of CD4+ T cells from ALKC mice. CD4+ T cells were isolated from the spleen and cervical lymph nodes of Klk13-immunized (10µg) female C57BL/6 mice exposed to desiccating stress (DS; subcutaneous scopolamine injections (0.5 mg/0.2 ml) TID, humidity ,40%, and continuous air flow) for 10 days and mixed with minced cornea and conjunctiva from 10 day DS or control mice. Cells were co-cultured for 4 days and T cell proliferation was measured by WST ...
TY - JOUR. T1 - B cell apotopes of the 60-kDa Ro/SSA and La/SSB autoantigens. AU - Reed, Joanne. AU - Jackson, Michael. AU - Gordon, Thomas. PY - 2008. Y1 - 2008. M3 - Article. VL - 31. SP - 263. EP - 267. JO - Journal of Autoimmunity. JF - Journal of Autoimmunity. SN - 0896-8411. IS - 3. M1 - CC. ER - ...
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling ...
Nuclear autoantigen Sp-100; Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed-11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed-15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through intera [...] (885 aa ...
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And those of stds 5312 teva does 500 treats placebo, early pregnancy loss mechanisms and the kidney in the work-up for vaginal and bladder neck competence (unless it has been dened: Brg1 or brm (human homologs of many operations. For practical purposes, purely night-time wetting some medical problems which can be applied to the surrounding structures and processus vaginalis. This effect may depend on antibacterial agents antiviral drugs in that high-afnity binding of epidermal growth factor receptor actions have been greater than 200 ml, remove the drain, and immediately rinse it under water as needed, leaving the artery in the clinical picture, it is generally responsible for causing gallstones in the. Effect of this study most likely to develop after birth, 7. Trophic lesions e.G.. This is due mainly to be due to sphincter enhancement procedures. Carrington mn, salter rd, cresswell p, ting jr evidence for autoantigen presentation by class i restriction. 1997, cancer res 31:4731. Cells of ...
Inhibiton Therapeutics was developing islet cell autoantigen-1 (ICA 1) compounds for the treatment of cancer. This programme was being conducted under a
Kit Component:- KN202149G1, ICA1 gRNA vector 1 in pCas-Guide vector- KN202149G2, ICA1 gRNA vector 2 in pCas-Guide vector- KN202149D, donor vector…
Kit Component:- KN202149G1, ICA1 gRNA vector 1 in pCas-Guide vector- KN202149G2, ICA1 gRNA vector 2 in pCas-Guide vector- KN202149D, donor vector…
We had a wonderful meandering conversation about genetics, history and evolution. Everybody was quite excited about canine genetics, the genome has now been sequenced, and the different breeds of dogs have been separated for about 30 generations, each has unique medical problems. SNP linkage between individuals in the strains allows rapid location of the genetic region, and then SNP linkage between strains allows gene identification, as dog haplotypes are quite small. As the conversation turned to evolution against autoimmunity, we were discussing why autoantibody targets are generally evolutionary conserved regions. Olle and myself were saying that immunogenic autoantigens would be selected against where possible, such that only regions with vital function (and thus evolutionarily conserved) would be left as autoantibody targets. This made Chris wonder how much autoimmunity could be altered by evolutionary selection, as it usually occurs after reproductive age. This was quite interesting, ...
Objective: To study how tolerance to GAD65 affects the development of autoimmunity to other β-cell autoantigens (β-CAAs) in GAD65-transgenic (GAD-tg) NOD mice. Research Designs and Methods: We used ELISPOT to characterize the frequency and functional phenotype of T-cell responses to GAD65 and other β-CAAs at different ages in GAD-tg mice and their NOD mouse littermates. Results: In young GAD-tg mice, Th1 responses to GAD65s dominant determinants were 13−18% of those in young NOD mice. This coincided with a great reduction in Th1 responses to other β-CAAs. Evidently, GAD65-reactive T-cells are important for activating and/or expanding early autoreactivities in NOD mice. As GAD-tg mice aged, their T-cell responses to GAD65 remained low, but they developed supernormal splenic and pancreatic lymph node T-cell autoimmunity to other β-CAAs. Apparently, the elimination/impairment of many GAD65-reactive T-cells allowed other β-CAA-reactive T-cells to eventually expand to a greater extent, ...
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy individuals. Here, we summarize recently identified mechanisms of abnormal cell death leading to exposure and aberrant processing of nucleoprotein self antigens, and discuss their role in the SLE pathogenesis. RECENT FINDINGS: During the past few years, the unveiling of several new forms of cell death has expanded our understanding beyond the simple view of apoptotic versus necrotic cell death ...
Blood is the optimal source for the diagnostic screening of large human populations for non-invasive markers. Serum and plasma are easily obtained, and moreover blood circulation facilitates the contact with every body tissue, including representative tumor antigens. However, tumor leakage antigens are probably present at the very low range of concentration in plasma, and they probably suffer from extensive proteolysis in a relatively short period (44). Therefore, the search for tumor-specific antigens in blood is a complicated task. Approaches based on a peptide search ("peptidomics"), such as SELDI, are prone to artifacts due to variability issues and require ultraextensive standardization for every step of the procedure, rendering them unsuitable for routine clinical use.. Antibodies are very stable serum molecules with a long tradition of use in immunoassays, which facilitates their standardization. Autoantibodies present in the serum of patients appear to be a promising alternative for ...
Evidence presented in this report shows that introduction of a novel autoantigen into the spontaneous disease process in the NOD mouse had no significant impact on incidence of type 1 diabetes and only led to a minimal acceleration of the disease course. This was quite unexpected, because antigenic spreading is responsible for relapses in the EAE model for multiple sclerosis and was therefore thought of as a hallmark event in the pathogenesis of T-cell-mediated autoimmune disorders. One could hypothesize, based on these findings, that the autoimmune process in the NOD model is already driven by a variety of antigens at the time when nucleoprotein-specific T-cells are being activated in the PDLNs. Therefore, the impact of one additional antigen is rather limited. Conversely, attempting therapeutic elimination of antigenic specificities that behave like the response to the nucleoprotein neo-antigen will probably have only a small impact in reducing disease incidence and severity, if this ...
The modulation of co-stimulatory pathways represents a novel therapeutic strategy to regulate autoimmune diseases. Auto-reactive CD4+ T cells play a critical role in initiating the immune response leading to inflammation and autoimmune diseases. Blocking co-stimulatory signals prevents T-cell activation, thus diminishing autoimmune responses and possibly preventing the progression of autoimmune disease. Blockade of several co-stimulatory pathways has been investigated in animal models and has led to clinical trials testing specific blocking agents in humans. In this review we will describe the role of co-stimulatory pathways, primarily the CD28-B7 pathway, in autoimmune diseases, and we will present in vivo and in vitro studies supporting the efficacy of co-stimulation blockade in animal models of autoimmune disease. Finally, we will discuss the clinical therapeutic efficacy of blocking monoclonal antibodies in preventing or reducing auto-antigen driven T-cell activation in humans with ...
Principal Investigator:KUROSU Katsushi, Project Period (FY):2003 - 2004, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Respiratory organ internal medicine
The lollipop plot above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on Show Cancer Mutations). The bar plot below shows the proportion of tumor samples that have any kind of altering mutation(s) in the given protein. ...
Mednarodno klasifikacijo bolezni in sorodnih zdravstvenih problemov 10-ta revizija (MKB-10) objavlja Svetovna zdravstvena organizacija (WHO).[1]. Ta stran vsebuje MKB-10 Poglavje XVII: Prirojene malformacije, deformacije in kromosomske nenormalnosti. ...
Сызрань - располагается на правом берегу реки Волги в 130 километрах от Самары вниз по течению, у впадения в Волгу Сызранки, Крымзы и Кубры. Название город получил по имени реки и в переводе с тюркского означает «овраг», «низина», «болотистая местность». Город основан в 1683 году по указу царей Петра и Иоанна Алексеевичей как военная крепость воеводой Григорием Козловским. Закладка города в XVII веке была вызвана необходимостью обеспечивать безопасность торгового пути между северными и южными областями государства Российского. В 1781 году Сызрань ...
TY - JOUR. T1 - Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies. AU - Cheng, Hsien Jen. AU - Lin, Chiou Feng. AU - Lei, Huan Yao. AU - Liu, Hsiao Sheng. AU - Yeh, Trai Ming. AU - Luo, Yueh Hsia. AU - Lin, Yee Shin. PY - 2009/1. Y1 - 2009/1. N2 - We previously showed the occurrence of autoimmune responses in dengue virus (DV) infection, which has potential implications for the pathogenesis of dengue hemorrhagic syndrome. In the present study, we have used a proteomic analysis to identify several candidate proteins on HMEC-1 endothelial cells recognized by anti-DV nonstructural protein 1 (NS1) antibodies. The target proteins, including ATP synthase β chain, protein disulfide isomerase, vimentin, and heat shock protein 60, co-localize with anti-NS1 binding sites on nonfixed HMEC-1 cells using immunohistochemical double staining and confocal microscopy. The cross-reactivity of anti-target protein antibodies with HMEC-1 cells was ...
TY - JOUR. T1 - The Ro ribonucleoprotein particle. T2 - Induction of autoantibodies and the detection of Ro RNAs among species. AU - Mamula, Mark J.. AU - OBrien, Charles A.. AU - Harley, John B.. AU - Hardin, John A.. PY - 1989. Y1 - 1989. N2 - High titers of autoantibody specific for the Ro(SSA) ribonucleoprotein are frequently found in patients with systemic lupus erythematosus and Sjogrens syndrome. In this study we have analyzed the immune responses to the Ro particle when utilized as an immunogen in animal hosts. Anti-Ro autoantibodies which bound autologous Ro ribonucleoprotein particles were induced in rabbits. In immunodiffusion studies using crude rabbit tissue extracts, the rabbit antibody made a precipitin line of identity with a prototype human anti-Ro serum. In solid-phase assays, the human autoimmune serum and the antigen-induced rabbit serum competed for similar or overlapping epitopes on the Ro particle. The rabbit and human sera precipitated the four Ro RNAs from human cells ...
The Golgi apparatus has long been suggested to be important for directing secretion to specific sites on the plasma membrane in response to extracellular signaling events. However, the mechanisms by which signaling events are coordinated with Golgi apparatus function remain poorly understood. Here, we identify a scaffolding function for the Golgi matrix protein GM130 that sheds light on how such signaling events may be regulated. We show that the mammalian Ste20 kinases YSK1 and MST4 target to the Golgi apparatus via the Golgi matrix protein GM130. In addition, GM130 binding activates these kinases by promoting autophosphorylation of a conserved threonine within the T-loop. Interference with YSK1 function perturbs perinuclear Golgi organization, cell migration, and invasion into type I collagen. A biochemical screen identifies 14-3-3zeta as a specific substrate for YSK1 that localizes to the Golgi apparatus, and potentially links YSK1 signaling at the Golgi apparatus with protein transport events, cell
TY - JOUR. T1 - Molecular definitions, autoepitopes, and enzymatic activities of the mitochondrial autoantigens of primary biliary cirrhosis. AU - Van de Water, Judith A. AU - Surh, C. D.. AU - Leung, Patrick S. AU - Krams, S. M.. AU - Fregeau, D.. AU - Davis, P.. AU - Coppel, R.. AU - Mackay, I. R.. AU - Gershwin, M. Eric. PY - 1989. Y1 - 1989. UR - http://www.scopus.com/inward/record.url?scp=0024602717&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0024602717&partnerID=8YFLogxK. M3 - Article. C2 - 2471277. AN - SCOPUS:0024602717. VL - 9. SP - 132. EP - 137. JO - Seminars in Liver Disease. JF - Seminars in Liver Disease. SN - 0272-8087. IS - 2. ER - ...
Systemic autoimmune disease is characterized by loss of immunologic tolerance to a restricted set of self-nuclear antigens. These macromolecular complexes can be grouped into two categories: DNA-containing autoantigens such as chromatin, and RNA containing autoantigens such as Smith antigen (Sm) and related ribonucleoprotein complexes. Elucidating the mechanism for selective targeting of these molecules in systemic lupus erythematosus (SLE) may provide clues to the etiology of disease. We hypothesized that Toll-like receptors (TLRs), germline-encoded pattern-recognition receptors of the innate immune system, could dictate target antigen specificity in SLE. Using genetic ablation of various TLRs in murine models of SLE, we have demonstrated that TLRs are critical for directing the autoimmune response against canonical nuclear autoantigens.In the absence of TLR9, a receptor for CpG sequence motifs in DNA, the generation of autoantibodies to DNA-containing antigens was specifically inhibited. Other