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M J Telen

Publications and source records attributed to M J Telen.

72 records · Page 4Linked to original sources
PubMed1988

Identification of human erythrocyte blood group antigens on decay-accelerating factor (DAF) and an erythrocyte phenotype negative for DAF.

Decay accelerating factor (DAF) is a glycoprotein present on the surfaces of many types ofcells in contact with plasma, including erythrocytes, leukocytes, and platelets (reviewed in reference 1). A small amount of DAF is also present in serum. Numerous investigators have demonstrated that DAF inhibits the action of C3 convertases on cell surfaces, and its absence has been shown to be at least partially responsible for the abnormal sensitivity to lysis by complement exhibited by erythrocytes of patients with the acquired stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) (2). Hereditary absence of DAF has not been previously described. Tc(a) and Cr(a) are high-frequency human erythrocyte antigens . These antigens are part of a family of blood group antigens, designated Cromer related, which are all absent from the null phenotype cell IFC(-) , or Inab (3). Recently, Spring and colleagues (4) have identified two monoclonal antibodies which bound to high frequency red cell antigens absent from the Inab phenotype. They also demonstrated that these antibodies, as well as several human antisera to Cromer-related antigens, bound to a 70-kD glycoprotein when used to stain immunoblots of human erythrocyte membrane proteins . Because the wide tissue distribution of mAb reactivity, along with some of the biochemical characterization and immunoblotting data, was similar to that of DAF, we investigated whether the Cromer-related antigens Cr(a) and Tc(a) resided on the DAF molecule.

Blood Group Antigens↗
PubMed1987

Human erythrocyte antigens. III. Characterization of a panel of murine monoclonal antibodies that react with human erythrocyte and erythroid precursor membranes.

Human erythrocyte membrane proteins express antigens which serve as markers for erythroid differentiation as well as targets for human blood group alloantibodies. We have produced and characterized a new panel of five monoclonal antibodies to erythrocyte membrane proteins. Three monoclonal antibodies (E3, E4, E5) were specific for erythrocyte glycophorins. One antibody (E3) identified the sialoglycoprotein alpha and beta homologous regions proximal to the plasma membrane, a second antibody (E4) was specific for sialoglycoprotein alpha, while a third (E5) was a sialoglycoprotein-beta-specific antibody. Two antibodies (E6 and TE10) to the 65,000-dalton chymotrypsin cleavage product of band 3 were also produced. These antibodies constitute a new panel of probes for investigation of normal erythroid differentiation, erythroleukemia, and the expression of normal and anomalous blood group antigens.

Animals↗
PubMed1987

Further characterization of erythrocyte p80 and the membrane protein defect of In(Lu) Lu(a-b-) erythrocytes.

We have previously shown that the In(Lu) gene down-regulates expression of an erythrocyte protein antigen identified by murine monoclonal antibody (MoAb) A3D8. In the present study we have examined In(Lu) Lu(a-b-) erythrocytes for expression of additional epitopes on the erythrocyte 80 kilodalton protein (p80) bearing the A3D8 antigen. Using a total of seven additional MoAbs that recognize three epitopes on erythrocyte p80, we have shown that In(Lu) Lu(a-b-) erythrocytes exhibit down-regulation of expression of all three epitopes. In(Lu) erythrocytes also showed a reduction in their reactivity to rabbit antibodies produced against purified p80 from either erythrocytes or lymphocytes. Furthermore the reactivity of the MoAbs was not altered by treatment of the cells with neuraminidase but was substantially reduced by treatment of cells with trypsin or chymotrypsin. The polyclonal anti-p80 sera were shown to react with a fragment of 50,000 daltons, still associated with erythrocyte ghosts, following treatment of the cells with trypsin or chymotrypsin. Treatment of erythrocytes with the thiol-reactive reagent AET decreased their reactivity with the MoAbs but had a variable effect on their reactivity with polyclonal antibodies. Erythrocyte p80 is a glycoprotein with N-linked oligosaccharides, as demonstrated by its binding to concanavalin A (Con A) and Len culinaris lectins. Following Endoglycosidase F treatment, erythrocyte p80 underwent a reduction in apparent mol wt of 11,000. The presence of a reduced amount of an intact p80 glycoprotein, seen by a decrease in reactivity with MoAbs directed at three distinct epitopes and with two different polyclonal antibodies, suggests that the In(Lu) gene interferes with expression by erythrocytes of the entire p80 glycoprotein.

Antibodies, Monoclonal↗
PubMed1986

Human medullary thymocyte p80 antigen and In(Lu)-related p80 antigen reside on the same protein.

Study of human T lymphocyte differentiation antigens with monoclonal antibodies has led to the identification of two antigens shared by erythrocytes and leukocytes. The protein (p80) defined by A1G3 antibody has previously been shown to be acquired during human intrathymic T-cell maturation. The antigen defined by A3D8 antibody has been demonstrated also to reside on an 80 kd protein; expression of the A3D8 antigen on erythrocytes and a subset of leukocytes is regulated by the rare In(Lu) gene. In this study, we demonstrate that the antigens defined by the A1G3 and A3D8 antibodies reside on the same protein and represent closely related but nonidentical epitopes on the p80 molecule. Expression of the A1G3 antigen on erythrocytes and a subset of leukocytes is also down-regulated by the In(Lu) gene. The possible role of the In(Lu) gene in thymocyte differentiation is discussed.

Antibodies, Monoclonal↗
PubMed1986

Separation of the acetylcholinesterase-deficient red cells in paroxysmal nocturnal hemoglobinuria.

Blood of patients with paroxysmal nocturnal hemoglobinuria (PNH) most often contains two or more populations of erythrocytes--one population with normal sensitivity to lysis by complement (PNH I cells) and a second population of moderately abnormal cells (PNH II cells) or markedly abnormal cells (PNH III cells). PNH II and III cells exhibit moderately and markedly increased sensitivity to lysis by complement, respectively, as well as other membrane defects. We have devised a method for isolating pure, intact PNH II and III cells from mixed populations by use of monoclonal antibodies and cell affinity chromatography. Study of purified cell populations has led to the identification of a further subtype, PNH IIIb, of PNH erythrocytes. PNH IIIb erythrocytes are less sensitive to complement lysis than PNH IIIa cells but are lysed by fluid-phase activation of complement, unlike PNH II erythrocytes.

Acetylcholinesterase↗
PubMed1985

An antibody to human thymic Hassall's body epithelium recognizes a subset of blood group A antigens.

TE-19, a mouse monoclonal antibody (mAb) against thymic Hassall's body epithelium, was investigated because of its cross-reactivity with human erythrocytes. Antibody TE-19 was found to react only with group A erythrocytes, though it reacted with Hassall's body epithelium from donors of all blood group phenotypes. TE-19 antibody bound preferentially to cells of subgroup A1, and reacted only weakly with A2 and Aint erythrocytes. Although it apparently bound to A antigen with both glycolipid and glycoprotein backbones, TE-19 antibody only reacted with A antigenic moieties containing long or branched chain structures. Analysis of TE-19 reactivity with erythrocyte membrane components using electroblotting and immunostaining techniques showed antibody reactivity with components migrating in the areas of band 4 X 5 and just ahead of the dye front, consistent with membrane glycolipid. It is possible that all human thymic Hassall's bodies contain epithelial cells which, irrespective of the donor's erythrocyte blood group, bear a carbohydrate antigen similar to A antigen.

ABO Blood-Group System↗
PubMed1985

The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane.

Paroxysmal nocturnal hemoglobinuria (PNH) is a myelodysplastic disease characterized by erythrocytes that show abnormally increased sensitivity to complement-mediated lysis. Complement-sensitive PNH erythrocyte membranes have previously been shown to lack acetylcholinesterase (AchE) activity, but the molecular basis of this deficiency has been unclear. We have used monoclonal antibodies to four different epitopes on the AchE molecule to show that abnormal PNH erythrocytes failed to bind these antibodies. Moreover, abnormal PNH erythrocytes contained no protein immunoprecipitable by these antibodies, while normal complement-insensitive erythrocytes from PNH patients showed normal amounts of immunoprecipitable AchE which had normal electrophoretic mobility. These data suggest that abnormal PNH erythrocytes lack AchE enzyme activity due to the absence of the AchE molecule from the cell membrane.

Acetylcholinesterase↗
PubMed1984

Increased efficiency of binding of nascent C3b to the erythrocytes of chronic cold agglutinin disease.

The pathogenesis of chronic cold agglutinin disease (CCAD) has been enigmatic. To determine if abnormal erythrocyte membrane constituents might provide the stimulus for antibody production, we compared the electrophoretic pattern of radiolabeled membrane glycoproteins of four patients with CCAD to that of normal control erythrocytes. For the CCAD erythrocytes, fluorographs revealed the appearance of an abnormal band whose molecular weight was estimated at 126,000 D. Using two-dimensional gel analysis and immunoblotting techniques, it was determined that the 126,000 D glycoprotein consisted predominately of polymeric glycophorin-alpha. Previous investigations had suggested that abnormalities in glycophorin-alpha influence the functional activity of the complement system. When purified complement (C)3 was activated in the fluid-phase by cobra venom factor complexes, CCAD erythrocytes bound nascent C3b 7-27 times more efficiently than normal erythrocytes. Normal erythrocytes could be induced to manifest the appearance of the 126,000 D band, and the increased efficiency of binding of nascent C3b by incubation with CCAD serum or with the purified cold agglutinin antibody plus autologous serum, but not with the purified antibody alone or the purified antibody plus EDTA-chelated autologous serum. These studies demonstrate that the interactions of IgM cold-reacting antibody and complement with glycophorin induce changes in the biophysical properties of the erythrocyte membrane which modify subsequent interactions with complement.

Anemia, Hemolytic, Autoimmune↗
PubMed1984

Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes.

We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western blot techniques that the antigen defined by A3D8 was on an 80-kD erythrocyte membrane protein. A second 170-kD protein was coprecipitated with the 80-kD protein but failed to show antigen activity by Western blot analysis. The 170-kD protein, when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in two dimensions, was composed of 50- and 30-kD disulfide-linked subunits. In(Lu) Lu[a-b-) erythrocytes differed from Lu(a+b+) or Lu(a-b+) erythrocytes in that In(Lu) deoxycholate erythrocyte membrane extracts contained trace amounts of immunoprecipitable 80-kD protein compared with detergent-solubilized erythrocyte membrane extracts prepared from Lu(a+b+) or Lu(a-b+) subjects.

Animals↗
PubMed1983

Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene.

Our study describes a novel human erythrocyte protein antigen, the expression of which is regulated by the rare Lutheran inhibitor In(Lu) gene. We have produced a monoclonal antibody (A3D8) that bound strongly to erythrocytes from subjects with Lutheran phenotypes Lu(a+b+), Lu(a+b-), and Lu(a-b+) but bound negligibly to erythrocytes from subjects with the dominant form of Lu(a-b-) phenotype, reflecting inheritance of the In(Lu) gene. Importantly, erythrocytes from an individual with the recessive form of Lu(a-b-) phenotype (i.e., absence of the In(Lu) gene and absence of genes encoding for Lutheran antigens) showed reactivity with A3D8 antibody comparable to that seen with Lu(a+) or Lu(b+) erythrocytes. A3D8 antigen activity was also found on all leukocytes and in serum and plasma; this activity also appeared to be regulated by the In(Lu) gene in serum, plasma, and on a subset of leukocytes. Thus, we have identified a human erythrocyte protein whose expression is modified by the In(Lu) gene. This knowledge that such an antigen exists on erythrocytes and in normal plasma should allow further studies into the molecular genetics of the In(Lu) gene and into the functional and structural significance of the A3D8 antigen.

Animals↗
PubMed1983

Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation.

The thymus is thought to be the primary central lymphoid organ in which T cells mature. Although thymic cortical and medullary compartments are distinct histologically, few antigens have been described that are absolutely acquired during the presumed intrathymic maturation pathway from cortical to medullary thymocytes. In this paper, we describe the acquisition during human intrathymic T cell maturation of a novel protein (p80) defined by a monoclonal antibody (A1G3). Although the p80-A1G3 antigen is distributed throughout the body and is not T cell specific, our study demonstrates that expression of p80-A1G3 antigen in normal human thymus is associated with thymocyte functional maturity and location in the thymus medulla. Moreover, in contrast to other markers of mature human T cells, the p80-A1G3 cell surface protein is not expressed on T6+ cortical thymocytes, and, therefore, is absolutely acquired by medullary thymocytes during T cell maturation. Thus, the p80-A1G3 antigen and the A1G3 antibody provide a heretofore unavailable system for the study of molecular events that transpire during the maturation of thymocytes.

Adolescent↗
PubMedDate not supplied

Human red cell antigens. IV. The abnormal sialoglycoprotein of Gerbich-negative red cells.

The minor red cell sialoglycoproteins--beta and gamma (also known as glycophorin C)--are believed to be important to the structural integrity of red cells. The absence of sialoglycoproteins alpha and delta, as seen in En(a-) and S-s-U- cells, respectively, results in cells with normal morphology, but the absence of sialoglycoproteins beta and gamma is associated with elliptocytosis. However, cells that lack Gerbich (Ge) antigens but have an abnormal sialoglycoprotein reactive with antibodies to beta have normal morphology. The authors used a monoclonal antibody specific for beta to explore the nature of this abnormal sialoglycoprotein and its interactions with other membrane proteins. The beta-like sialoglycoprotein of Ge-Yus- red cells appears to react poorly with some antibodies due to steric hindrance by other molecules of sites normally available to immune agglutinins. This steric hindrance is not due to a single interaction with either sialoglycoprotein alpha or delta or band 3. Furthermore, steric hindrance by other molecules does not account for the lack of Ge antigens on these cells.

Antibodies, Monoclonal↗
PubMedDate not supplied

Human red cell antigens. V. Expression of In(Lu)-related p80 antigens by recessive-type Lu(a-b-) red cells.

The In(Lu) gene, which inhibits the expression of Lutheran blood group antigens by red cells (RBCs), also down-regulates the expression of an 80-kD glycoprotein, In(Lu)-related p80, by both RBCs and a subset of white cells. This study examined the expression of multiple-RBC p80 epitopes by autosomal and X-linked recessive-type Lu(a-b-) RBCs in order to explore the relationship, if any, between expression of In(Lu)-related p80 and Lutheran antigens. Both autosomal and X-linked types of recessive Lu(a-b-) RBCs expressed near-normal to increased amounts of p80 antigens, as measured by radioimmunoassay. P80 from both types of recessive Lu(a-b-) RBCs had apparently normal molecular weight in denaturing polyacrylamide gels and showed normal sensitivity to digestion by trypsin and chymotrypsin. Thus, the absence of Lutheran antigens on recessive-type Lu(a-b-) RBCs is not associated with decreased or absent p80 antigens. Furthermore, the XS2 gene probably does not act via a mechanism similar to that of the In(Lu) gene, since the expression of p80 remains undiminished in X-linked recessive-type Lu(a-b-) RBCs.

Genes, Recessive↗
PubMedDate not supplied

JMH variants: serologic, clinical, and biochemical analyses in two cases.

BACKGROUND: JMH is a high-frequency red cell blood group antigen that resides on a 76- to 80-kDa glycosylphosphatidylinositol-linked protein also known as CDw108. Antibodies with JMH specificity are often autoimmune and are usually, if not always, clinically benign. Some individuals with JMH-variant antigen produce alloantibodies to JMH, but little evidence concerning their clinical significance is available. This article reports on two patients who express a JMH-variant antigen and produced alloanti-JMH. STUDY DESIGN AND METHODS: Murine monoclonal antibodies and human antibodies to JMH were used in hemagglutination, radioimmunoassay, and Western blot testing of red cells from two JMH-variant patients; antiserum from one of these patients was also used in biochemical studies. In addition, in vivo survival of JMH-positive red cells was studied in the same patient. RESULTS: Biochemically, both examples of red cells with the JMH-variant phenotype expressed a JMH protein with a molecular weight similar to that of the normal JMH protein. For both patients, family studies suggested an autosomal recessive pattern of inheritance. Survival study demonstrated reduced in vivo red cell survival in one patient. CONCLUSION: JMH-variant phenotypes express a protein of normal molecular weight and are inherited in an autosomal recessive pattern. Furthermore, individuals with this phenotype can produce clinically significant antibodies.

Aged↗