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G Lindahl

Publications and source records attributed to G Lindahl.

At least 19 recordsLinked to original sources
PubMed1992

Two major classes in the M protein family in group A streptococci.

The M protein family of molecules in the group A streptococcus comprises a number of cell surface proteins that interact with the immune system of the host. One of the proteins in this family is the IgA receptor Arp4, which has C repeats similar to those that characterize the known M proteins. The streptococcal strain expressing Arp4 also expresses a second immunoglobulin-binding protein, Mrp4, which is shown here to be encoded by a gene located immediately upstream of the gene for Arp4. In addition to binding IgG, Mrp4 also binds fibrinogen, a property ascribed to M proteins. DNA sequence analysis demonstrated that the Mrp4 protein indeed is a member of the M protein family, but it was unexpectedly found to have a type of repeat that is identical to the A repeat described for FcRA76, a partially sequenced streptococcal Fc receptor. Purified FcRA76 was shown to bind fibrinogen and IgG, like Mrp4. These data show that the known molecules in the M protein family can be divided into two classes, A and C, according to the type of repeat region found. Hybridization studies with a panel of clinical isolates indicate that many streptococcal strains express class A and class C proteins, whereas some strains express only class C proteins. Class A molecules show amino-terminal sequence variation, like class C molecules, which suggests that proteins of both classes are targets for the immune response.

Amino Acid Sequence↗
PubMed1992

Protein Arp and protein H from group A streptococci. Ig binding and dimerization are regulated by temperature.

Cell surface proteins that bind to the Fc part of Ig are expressed by many strains of group A streptococci, an important human pathogen. Two such bacterial strains, AP4 and AP1, were shown to bind IgA and IgG, respectively, in a temperature-dependent manner. The binding of radiolabeled Ig to the bacterial cells was lower at 37 degrees C than at 22 and 4 degrees C. Similarly, protein Arp, the IgA-binding protein isolated from strain AP4, and protein H, the IgG-binding protein isolated from strain AP1, displayed a strong Ig-binding at 22 degrees C and lower temperatures, and virtually no binding at all at 37 degrees C. The effect was reversible: lowering of the temperature restored the binding and vice versa. A gradual shift between binding and nonbinding took place between 27 and 37 degrees C. Gel chromatography and velocity sedimentation centrifugation showed that protein Arp and protein H appeared as noncovalently associated dimers at 10 and 22 degrees C, and as monomers at 37 degrees C. These results strongly suggest that the dimerization of protein Arp and protein H, rather than the low temperature itself, yielded the strong Ig-binding of the proteins at 10 and 22 degrees C. Indeed, after covalent cross-linking of the dimers at 10 degrees C by incubation with low concentrations of glutaraldehyde, full Ig-binding was achieved even at 37 degrees C. A carboxyl-terminal proteolytic fragment of protein Arp, which completely lacked the IgA-binding capacity at any temperature, showed the same temperature-dependent dimerization as intact protein Arp, suggesting that the Ig-binding part of the protein is not required for dimerization. The implications of these results for the function of Ig-binding group A streptococcal proteins, and their role in the host-parasite relationship are discussed.

Bacterial Proteins↗
PubMed1992

Many group A streptococcal strains express two different immunoglobulin-binding proteins, encoded by closely linked genes: characterization of the proteins expressed by four strains of different M-type.

Most group A streptococcal strains are able to bind immunoglobulin (Ig) in a non-immune manner, and the majority of these strains bind both IgA and IgG. Using molecular cloning and immunochemical techniques, we have purified and characterized the Ig Fc-receptors expressed by four such strains. Two of the strains express a novel type of receptor, designated protein Sir, which binds IgA and IgG of all subclasses, and therefore has broader reactivity than any Fc-receptor previously described. The other two strains express protein Arp, a receptor that binds IgA of both subclasses, and also binds polyclonal IgG weakly. Characterization of the weak IgG-binding ability of protein Arp shows that it binds only some monoclonal IgG proteins, in particular those of the IgG3 subclass. The four strains studied here were unexpectedly found to also express a second Ig-receptor, called protein Mrp, encoded by a gene closely linked to the gene for the first receptor. The Mrp protein does not bind IgA, but it binds IgG molecules of the IgG1, IgG2 and IgG4 subclasses, and it also binds fibrinogen. Binding of fibrinogen has been reported to be a characteristic property of streptococcal M proteins, which suggests that the Mrp protein may be an M protein that also binds Ig. Taken together, all available evidence now indicates that most strains of group A streptococci express two different Ig-binding proteins, encoded by closely linked genes.

Amino Acid Sequence↗
PubMed1991

Molecular characterization of an IgA receptor from group B streptococci: sequence of the gene, identification of a proline-rich region with unique structure and isolation of N-terminal fragments with IgA-binding capacity.

Certain strains of group B streptococci express a cell surface protein that binds IgA and acts as a virulence factor. This IgA receptor is referred to here as protein Bac. The gene for protein Bac was cloned and expressed in Escherichia coli, and the complete nucleotide sequence was determined. The deduced amino acid sequence of 1134 residues includes a signal sequence of 37 amino acids and a putative membrane anchor region at the C-terminal end. The processed form of the receptor, 1097 residues, has a calculated molecular weight of 123,786. There are no cysteines in protein Bac, suggesting a fibrillar structure. The C-terminal half of the protein includes a 90 residues long region with a novel type of periodic structure, the "XPZ motif", in which every third amino acid is proline. Unlike other bacterial immunoglobulin-binding proteins, there are no long repeats in protein Bac. Clones which express only part of the protein Bac gene were used to show that IgA-binding takes place in the N-terminal part of the molecule. Protein Bac was originally described as an antigen called beta, but N-terminal fragments that bind IgA do not react with a reference serum against the beta antigen. These and other data indicate that protein Bac can be divided into two regions with different functions: an N-terminal IgA-binding region and a C-terminal region corresponding to the beta antigen. The IgA-binding region of protein Bac does not show any homology to protein Arp, the IgA receptor from group A streptococci, although these receptors have similar binding properties. This indicates that convergent evolution has favored the appearance of these two structurally different streptococcal IgA receptors.

Amino Acid Sequence↗
PubMed1991

Pancreatic autoantibodies and pancreatic function in Sjögren's syndrome.

Pancreatic autoantibodies were determined in 49 patients with Sjögren's syndrome and related to functional parameters. Pancreatic duct autoantibodies (PDA) were detected in the sera of three patients, and all showed abnormal exocrine pancreatic function. Islet cell antibodies (ICA) were not detected in the sera of the 49 patients, including two individuals with diabetes mellitus. In conclusion, PDA occur in patients with Sjögren's syndrome, and may be associated with exocrine pancreatic dysfunction.

Autoantibodies↗
PubMed1990

Characterization of an IgA receptor from group B streptococci: specificity for serum IgA.

Some strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA-Sepharose affinity chromatography. The sequence of the N-terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 x 10(8) M-1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, alpha 1-microglobulin-IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed.

Amino Acid Sequence↗
PubMed1990

Variation in the size of human apolipoprotein(a) is due to a hypervariable region in the gene.

We have investigated whether the size heterogeneity of the human apolipoprotein(a) [apo(a)] is due to differences in the number of plasminogen kringle 4-like repeat units present in the different alleles. Using the Southern blot hybridization technique and a DNA probe for the kringle 4 domain of plasminogen, we have observed that in 31 different individuals a 5.8-kb PvuII restriction fragment band varies widely in intensity relative to other bands. A strong correlation (r = 0.76, P less than 0.001) was found between apo(a) protein size and the variation in intensity of the detected restriction fragment band. We confirmed this correlation in a large family where the parents are heterozygous for the apo(a) protein size isoforms. The specificity of the 5.8-kb band was established by using an apo(a)-specific oligonucleotide. These correlations strongly suggest that the observed size heterogeneity in apo(a) protein is due to different numbers of copies of the kringle 4 sequence in the apo(a) glycoprotein gene.

Alleles↗
PubMed1990

Binding of IgA and/or IgG is a common property among clinical isolates of group A streptococci.

Certain strains of group A streptococci are known to bind IgA and/or IgG via a cell surface receptor, which may act as a virulence factor. The distribution of such receptors among routine clinical isolates was studied, using a total of 225 strains and an assay based on the binding of radiolabelled immunoglobulins. Among 194 throat strains isolated during three different time periods in two different geographical areas of Sweden, 82% showed significant binding of IgA and/or IgG. Studies on 31 septicaemia strains, isolated over a period of more than 8 years, showed binding for 84% of the isolates. The binding strains were of several different T-types and could be subdivided into two groups, those binding both IgA and IgG and those binding IgG only. These data show that binding of IgA and/or IgG is a very common property among clinical isolates of group A streptococci.

Antigens, Differentiation↗
PubMed1990

Signs of Sjögren's syndrome in a patient with myasthenia gravis.

A case of myasthenia gravis (MG) with recurrent submandibular salivary gland enlargement and focal lymphocytic infiltrates in lip salivary glands is described. Though the clinical and close histopathological resemblance with Sjögren's syndrome (SS), a condition characterized by impaired exocrine function of affected glands, no exocrine disturbance evolved during 3-years follow up. The clinical and histopathological overlap between MG and SS, sharing several immunological characteristics, might be of relevance in further studies on the pathogenesis of the two conditions.

Adult↗
PubMed1990

Variation of MHC class I and II antigen expression in relation to lymphocytic infiltrates and interferon-gamma positive cells.

The occurrence of MHC antigens on epithelial cells in lip salivary glands obtained from patients with various connective tissue diseases and from bone marrow recipients was studied. The amount of infiltrating lymphocytes correlated to an increase in MHC class I and II antigen expression, but not to diagnosis or glandular function. Interferon-gamma + infiltrating cells were scanty. The role of interferon-gamma as the main inducer of MHC antigens and the notion "aberrant" HLA-DR thought to perpetuate chronic autoimmune disease are questioned.

Adolescent↗
PubMed1989

The gene for the Lp(a)-specific glycoprotein is closely linked to the gene for plasminogen on chromosome 6.

We have studied the segregation of the Lp(a) glycoprotein phenotypes and of the plasminogen (PLG) polymorphism in three two-generation families. The inheritance of the Lp(a) gene was followed using the Lp(a) glycoprotein size polymorphism and that of the plasminogen gene, using protein and DNA polymorphisms. In the three families studied, no recombination was observed in 18 meioses. The lod score for linkage between the Lp(a) glycoprotein locus and the plasminogen locus in these families is greater than 5.0 at a recombination fraction of theta = 0. Our results show that the structural gene for the Lp(a) glycoprotein is closely linked to the gene for plasminogen on chromosome 6.

Chromosomes, Human, Pair 6↗
PubMed1989

Cell surface proteins of a group A streptococcus type M4: the IgA receptor and a receptor related to M proteins are coded for by closely linked genes.

Two genes coding for cell surface proteins were cloned from a group A streptococcus type M4: the gene for an IgA binding protein and the gene for a fibrinogen binding protein. Both proteins were purified and partially characterized after expression in Escherichia coli. There was no immunological cross-reaction between the two proteins. The IgA binding protein, called protein Arp4, is similar to an IgA receptor previously purified from another strain of group A streptococci, but the proteins are not identical. Characterization of many independent clones showed that the two proteins described here are coded for by closely linked genes. Bacterial mutants have been found which have simultaneously lost the ability to express both genes, and a simple method to isolate such mutants is described. The existence of these variants indicates that expression of the two cell surface proteins may be coordinately regulated. Binding of fibrinogen is a characteristic property of streptococcal M proteins, and the available evidence suggests that the fibrinogen binding protein is indeed an M protein.

Antigens, Bacterial↗
PubMed1989

Lymphocytic infiltrations of lip salivary glands in bone marrow recipients. A model for the development of the histopathological changes in Sjögren's syndrome?

By use of a PAP staining technique, the immunohistopathology in repeated biopsies from the lip salivary glands (LSGs) from patients undergoing bone marrow transplantation (BMT) was studied. In the previously normal LSGs, focally arranged lymphocytes and adjacent epithelial DR-expression appeared within 12 weeks post BMT, reaching a maximum between 26 and 52 weeks post BMT. Two years post BMT, lymphocytic infiltrates and epithelial DR-expression were still present in half of the specimens but were not seen in the remaining ones. The immunohistopathological changes seen in LSGs post BMT were indistinguishable from what has been found in Sjögren's syndrome. The appearance, and in some patients the subsequent disappearance, of the lymphocytic infiltrates and the epithelial DR-expression, without correlation to clinical symptoms of chronic graft-versus-host disease or immunosuppressive treatment, emphasizes the dynamic nature of lymphocytic infiltration of LSGs in BMT patients. Whether this also pertains to naturally occurring Sjögren's syndrome remains to be elucidated.

Bone Marrow Transplantation↗
PubMed1989

Lymphocytic infiltrates and epithelial HLA-DR expression in lip salivary glands in connective tissue disease patients lacking sicca: a prospective study.

Focal lymphocytic infiltrations indistinguishable from what has been described in Sjögren's syndrome (SS) were found in lip salivary gland (LSG) biopsies in 15 of 80 patients with various connective tissue diseases (CTDs) lacking sicca. During a 4-year follow-up period, none of the patients developed symptoms or signs of decreased lacrimal or salivary gland function. Focal lymphocytic infiltrates of LSGs seemingly unrelated to glandular function are to be found in patients' various CTDs and therefore the diagnostic value of a positive LSG biopsy in this context has to be questioned.

Adult↗
PubMed1989

Extensive sequence homology between IgA receptor and M proteins in Streptococcus pyogenes.

Many strains of Streptococcus pyogenes are known to express a receptor for IgA. The complete nucleotide sequence of the gene for such a receptor, protein Arp4, has been determined. The deduced amino acid sequence of 386 residues includes a signal sequence of 41 amino acids and a putative membrane anchor region, both of which are homologous to similar regions in other streptococcal surface proteins. The processed form of the IgA receptor has a length of 345 amino acids and a calculated molecular weight of 39544. The N-terminal sequence of the processed form is different from that previously found for a similar IgA receptor isolated from a S. pyogenes strain of type M60. The sequence of protein Arp4 shows extensive homology to the C-terminal half of streptococcal M proteins, but not to the streptococcal IgG receptor protein G or staphlyococcal protein A. Apart from the membrane anchor, this homology includes a sequence of 119 amino acid residues containing three repeated units and a 54-residue sequence without repeats. The protein expressed in Escherichia coli is found in the periplasmic space, in which it constitutes the major protein. Protein Arp4 is the first example of a surface protein that has both immunoglobulin-binding capacity and structural features characteristic of M proteins.

Amino Acid Sequence↗
PubMed1989

Receptor for IgA in group A streptococci: cloning of the gene and characterization of the protein expressed in Escherichia coli.

The gene for an IgA-binding protein from a group A streptococcal strain was cloned and expressed in Escherichia coli. The IgA-binding protein, called protein Arp, was purified on IgA-Sepharose, allowing complete purification in a single step. Analysis of protein Arp by Western immunoblotting demonstrated a major IgA-binding band, with an apparent molecular weight of 42 kD. The purified protein was shown to bind serum IgA and secretory IgA, as well as monoclonal IgA of both subclasses. There was no binding to IgM, IgD or IgE, but a weak binding to IgG. Inhibition experiments with whole bacteria indicated that IgA and IgG bind at separate sites. Experiments with immunoglobulin fragments showed that protein Arp binds to the Fc region of both IgA and IgG. The equilibrium constant of the reaction between protein Arp and polyclonal human IgA was determined to be 5.6 x 10(8) M-1. Amino acid sequencing of protein Arp demonstrated a direct repeat of 7 amino acids in the NH2-terminal region, a feature previously found in several streptococcal M proteins. This suggests that protein Arp, like M proteins, may be a streptococcal virulence factor.

Amino Acid Sequence↗