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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of evidence for structural similarity of variable region genes of anti-DNA and anti-(T,G)-A-L antibodies, polyspecific interactions of monoclonal anti-DNA and anti-(T,G)-A-L antibodies were investigated. Of 20 monoclonal antibodies from C57BL/10 mice with (T,G)-A-L binding, two bound DNA as determined by ELISA. In contrast, two of five anti-DNA monoclonal antibodies from MRL-lpr/lpr mice bound (T,G)-A-L. For both sets of antibodies, antigen binding was shown to be the activity of the same antibody by cross-inhibition studies. To determine whether such polyspecific antibodies were expressed during autoimmune disease, sera of autoimmune MRL-lpr/lpr mice were tested for anti-(T,G)-A-L activity. This analysis demonstrated minimal elevations of anti-(T,G)-A-L in comparison to BALB/c controls. These studies thus confirm predictions about the binding activity of anti-(T,G)-A-L and anti-DNA antibodies based on structural analysis of variable region genes. They further indicate, that while anti-(T,G)-A-L and anti-DNA antibodies may have overlapping specificity, polyspecific antibodies of this kind are not preferentially expressed during autoimmunity.
Mol Immunol 1987 Apr
PMID:Characterization of monoclonal antibodies with specificity for DNA and the synthetic polypeptide antigen (T,G)-A-L. 349 82

Insulin-dependent diabetes mellitus is an autoimmune disease the development of which is influenced by genetic factors (Cahill & McDevitt, 1981). As concordance for IDD is less than 50% in identical twins, environmental factors are also required for the development of IDD. Although viral agents have been implicated in the past, the specific environmental components leading to IDD remain unknown. This paper reviews current research focused on the genetic factors that influence susceptibility to IDD.
Mol Biol Med 1986 Apr
PMID:Molecular genetics of insulin-dependent diabetes mellitus. 352 80

Systemic autoimmune disease states are known to be associated with abnormal cell growth or differentiation. In the murine models of systemic lupus erythematosus (SLE), specific genotypes result in dysregulated growth of certain lymphocyte subpopulations. Although genes underlying autoimmune syndromes have been characterized by mendelian genetics, it has not yet been possible to characterize them at the molecular level. Recently, it has become clear that cellular proto-oncogenes can regulate cell growth and differentiation. Therefore, we have studied the expression of five different proto-oncogenes; myc, myb, abl, bas, and raf, in organs and cells of various autoimmune strains. These genes were selected because each has previously been associated with abnormal hemopoietic cell growth, and because each has been at least partially characterized at the molecular and functional level. We have found selective abnormal proto-oncogene expression associated with the characteristic abnormal cell growth or differentiation of lymphocytes of autoimmune mice. The lymph nodes of MRL-lpr/lpr mice are packed with unusual T cells. These had a marked increase in myb expression. There was a 20-40-fold increase in myb RNA in lymph nodes of lpr/lpr mice on several different genetic backgrounds. The gld/gld mouse has a very similar unusual T cell in the lymph nodes: it also had a comparable increase in myb RNA in the nodes. In contrast, myb expression was not elevated in the other autoimmune mouse strains lacking these abnormal T cells. Whereas such lpr/lpr mice had increased myb expression in the lymph nodes and splenic T cells, they had markedly subnormal myb expression in the thymus, an organ with high myb in normal and in the other autoimmune strains. These results suggest that one phase of intrathymic differentiation in other mice occurs in the periphery of lpr/lpr mice. The spleens of NZB and male BXSB mice had increased myc expression which was found to be associated with B cells upon cell separation. Similarly, increased bas and abl expression was associated with autoimmune B cells. The xid gene, which retards or prevents the expression of murine lupus by retarding B cell maturation, was associated in BXSB.xid, NZB.xid, and MRL-lpr/lpr.xid congenic mice with marked reduction in expression of myc, bas, and abl in the spleens containing B cells, but not of myb in the lpr/lpr.xid nodes containing primarily the unusual T cells. Raf expression was found to be associated in lpr/lpr and gld/gld mice with both the unusual T cells and splenic B cells.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1985
PMID:Oncogene expression in autoimmune mice. 391 23

Antibodies directed against soluble cellular antigens are a distinctive feature of systemic autoimmune disease. We have examined 22 autoantibodies in sera from 1111 patients and present the disease associations together with a biochemical analysis of the antigens. The data emphasize the clinical specificity of the antibodies and the restricted number of cellular components that commonly elicit an immune response. In several instances, serological relationships between antibodies mirror biochemical relationships between the corresponding antigens. The antigens are mainly proteins and are often present in complexes with additional protein or nucleic acid molecules. In myositis the antibodies react chiefly with cytoplasmic antigens such as aminoacyl-tRNA synthetases, in contrast to the mainly antinuclear response in SLE. It is argued that both environmental stimuli and genetic factors govern autoantibody specificity, and that molecular characterization of the cellular antigens may yield clues to the aetiology of the disease and of the concomitant, specific autoimmune response.
Mol Biol Med 1984 Apr
PMID:Cellular protein and RNA antigens in autoimmune disease. 608 92

Recent knowledge on snRNPs is reviewed in this paper. The relevant findings of our laboratory were essentially as follows: Particles containing small nuclear RNAs (snRNAs) were characterized ten years ago. More recently Lerner et al. have shown that particles containing snRNAs react with antibody produced in autoimmune disease. Furthermore, the snRNA (some of them are probably involved in 'splicing') were found associated with hnRNP. In the present work we have studied structures, extracted from hnRNP that contain snRNAs. We were able to obtain and purify ribonucleoproteins complexes containing some of the snRNAs. These particles (snRNPs) are very stable. They were purified by three different successive cycles of centrifugation under denaturing conditions. The particles are characterized by a density of 1,43 g/cm3 in CsCl and a sedimentation coefficient of 11--12S. They contain five species of snRNAs (U1, U2, U4, (U5), U6 according to the nomenclature of Lerner et al.) and at least one polypeptide with a molecular weight of about 15000 daltons. An other particle containing only U5 was also isolated. These snRNPs are not disaggregated in media destabilizing ionic forces, hydrophobic interaction or hydrogens bonds and seem to different from the snRNPs described by Lerner et al.
Mol Biol Rep 1981 May 22
PMID:Particles containing small molecular weight nuclear RNAs (snRNPs). Structure and possible functions. 616 52

Hybridoma technology has paved the way for new insights into mechanisms of autoimmunity and autoimmune disease. Autoantibodies and autoantigens can now be studied at the level of the individual molecule. The specificity of the autoimmune reaction, as well as its pathogenetic role in disease, may be more accurately assessed. Monoclonal autoantibodies which bind to red blood cells, IgG, DNA, RNA and ribonucleoprotein complexes have been prepared by several groups of investigators. The initial molecular and functional characterization of these immunoglobulins and their corresponding antigens is described.
Mol Immunol 1982 Jul
PMID:Monoclonal autoantibodies: an approach to studying autoimmune disease. 618 95

We have employed sera from patients with autoimmune disease to characterize the nuclear SS-B/La antigen in uninfected and adenovirus-infected KB cells. A 45,000-dalton phosphorylated polypeptide was specifically precipitated with anti-SS-B sera, and the level of phosphorylation was increased after infection. The increased phosphorylation appears to occur at the same amino acid residues phosphorylated in uninfected cells and results from increased phosphorylating activity rather than from altered enzyme specificity. A competition experiment between infected and uninfected cell extracts indicates that the antigen in the infected cell binds more strongly to SS-B/La antibodies. Fragments of adenovirus-induced virus-associated RNA as well as intact molecules complex with SS-B/La antigen and are immune precipitated with autoimmune sera.
Mol Cell Biol 1983 Jul
PMID:Characterization of a phosphoprotein associated with the SS-B/La nuclear antigen in adenovirus-infected and uninfected KB cells. 619 14

A new system for the rapid production at high frequency (greater than 10(-5] of stable human hybridomas is described. This system is based on a high efficiency fusion variant human lymphoblastoid cell line designated WI-L2-729-HF2 and is comparable in many ways to commonly used murine hybridoma systems. WI-L2-729-HF2 cells fuse at high frequency with mitogen-stimulated human b cells resulting in the rapid appearance (within 2 weeks) of stable hybridomas in hypoxanthine/aminopterin/thymidine (HAT) medium. Whereas the WI-L2-729-HF2 cell line secretes only trace levels (50 to 100 ng/ml) of an IgG,kappa and has surface IgM,kappa, HAT-resistant hybridomas secrete high levels (10 to 20 micrograms/ml) of new human immunoglobulins, including immunoglobulins containing alpha or lambda chains not found in the tumor parental cell line. These hybridomas have remained stable for over four months in continuous culture, secreting high levels of new immunoglobulins in both conventional and serum-free medium, a feature which makes possible large-scale production and purification of human antibodies. This system has the potential to provide tools and reagents for investigations involving, for example, the diagnosis and treatment of human autoimmune disease and cancer.
Mol Biol Med 1983 Sep
PMID:The WI-L2-729-HF2 human hybridoma system. Stable hybrids at high frequency. 633 16

16 alpha-Hydroxyestrone (16 alpha OHE) has been shown previously to react nonenzymatically with proteins via a Heyns rearrangement of a Schiff base intermediate. Albumin modified by the addition of 16 alpha OHE is immunogenic, despite a relatively low molar substitution. High-titre antisera can be elicited which have a very high affinity toward the estrogen hapten. Cross-reactivity analysis reveals a high specificity for the phenolic A-ring and a lack of specificity to chemical substituents in the D-ring, the site of covalent linkage. The antisera reacts equally well with 16 alpha OHE-peptides as with 16 alpha OHE-lysine, suggesting the utility of this antisera in analyzing either enzymatically or chemically hydrolyzed proteins for the presence of 16 alpha OHE adducts. Immunochemical analysis of proteins modified by 16 alpha OHE may provide insight into the pathogenesis of systemic lupus erythematosus, an autoimmune disease in which elevated levels of 16 alpha OHE are known to occur.
Mol Immunol 1983 Dec
PMID:Characterization of antisera to the addition product formed by the nonenzymatic reaction of 16 alpha-hydroxyestrone with albumin. 665 75

The NZB/NZW F1 murine model for the autoimmune disease systemic lupus erythematosus (SLE) has been employed in somatic cell hybridizations to develop hybridoma autoantibodies with double-stranded (ds) DNA specificity. Monoclonal anti-DNA antibodies from one hybridoma cell line were purified and analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing. Results of comparative binding studies with tritiated [3H]-colicin E1 plasmid DNA probes suggested preferential binding for the native DNA conformation relative to single-stranded DNA. [3H]dsDNA binding was inhibited by several ribohomopolymers (poly G, U and I) but not by free nucleotides, indicating that the phosphodiester-ribose backbone may contribute to the binding specificity of the clonotype.
Mol Immunol 1982 Jun
PMID:Monoclonal murine anti-nucleic acid antibody with double-stranded specificity. 698 Oct 61


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