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PubMed2000

Identification of epitopes for cross-reaction, auto-reaction and autoantibodies to catalase.

We identified in bovine and rat catalase two epitopes that were responsible for a cross-reaction between the two species using cross-reactive antibodies raised in rabbits by immunization with their respective catalases. The epitopes were(444)TFYLK(448)and(458)LCENIAGHLK(467)in bovine catalase and(445)TFYTK(449)and(459)LCENIANHLK(468)in rat catalase. The two epitopes in rats were also identified as epitopes for auto-reactive antibodies that were raised in rats by immunization with bovine catalase and were reactive with a homologous rat catalase. Furthermore, one of the rat epitopes,(459)LCENIANHLK(468), was identified as the epitope for autoantibodies which were inducible by intensive immunization in rats with the homologous rat catalase. A possible implication of the epitopes in certain human diseases is discussed.

Amino Acid Sequence↗
PubMed1999

Epitope structures recognised by antibodies against the major coat protein (g8p) of filamentous bacteriophage fd (Inoviridae).

To map the accessible surface of filamentous bacteriophage fd particles, the epitope structures of polyclonal rabbit serum and three mouse monoclonal antibodies raised against complete phage were analysed. Western blot analysis confirmed the major coat protein, gene VIII product (g8p or pVIII), to be the antigen. Overlapping peptides were synthesised by spot synthesis on cellulose membranes, covering the whole sequence of g8p. Each of the three tested monoclonal antibodies, B62-FE2, B62-GF3/G12 and B62-EA11, reacted with a core epitope covering ten amino acid residues at or near the amino terminus of g8p. The epitope recognised by B62-FE2 consists of the ten N-terminal amino acid residues of g8p. Extension of the amino terminus by various sequences did not inhibit binding, indicating that a terminal amino group is not essential for the interaction. Both B62-GF3/G12 and B62-EA11 recognise internal epitopes covering amino acid residues 3 to 12 of g8p. The epitopes of the polyclonal rabbit serum were also confined to the 12 N-terminal amino acid residues. The contribution of individual amino acid residues to the binding was analysed by a set of peptides containing individual amino acids exchanged by glycine. Accessible residues were Glu2, Asp4, Asp5, Pro6, Lys8, Phe11 and Asp12. The positions of the essential amino acid residues within the epitope are in accordance with a helical conformation of the amino-terminal region of g8p. Further, the results suggest new designs of phage display screening vectors to improve their performance in analysing non-linear epitopes.

Amino Acid Sequence↗
PubMed2000

Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice.

We investigated the antigenic specificity of the humoral immune response to infection by Salmonella typhimurium, by competitive inhibition enzyme-linked immunosorbent assay and Western immunoblots. A panel of eight murine monoclonal antibodies, raised to OmpC and OmpD porins and lipopolysaccharide (LPS)-O antigens, was used to define the specificity of the polyclonal immune response in mice. The monoclonal antibody panel recognized five distinct epitopes; these were localized to surface-exposed loops of OmpC and OmpD porin, to the "eye-let" forming loop L3 of OmpC/OmpD, and to LPS-O4 and O5 factors. The immune mouse serum raised to infections with S. typhimurium LT-2 strain WB600 (wild-type) competitively inhibited the binding of biotin-labelled monoclonal antibodies to the epitopes that they recognize, indicating that all five epitopes were targets of the host immune response to natural infection. However, only two epitopes, one within a surface-exposed loop of OmpC porin, and the other in the LPS-O4 factor, were immunodominant. Furthermore, the bacterial LPS core and O-antigen structure influenced the immune response to the porins. Surface epitopes of porins were dominant in the rough strain SH5014 (rfa), whereas the immune recognition of LPS epitopes was predominant in mice infected with the smooth, wild-type strain (WB600). Finally, the immune response to LPS epitopes O4 and O5 was more pronounced in mice immunized with heat-killed cells than those infected with live S. typhimurium.

Animals↗
PubMed1993

Characterization of B-cell epitopes in the envelope glycoproteins of simian immunodeficiency virus.

We identified previously a neutralizing epitope in the V2 domain of the simian immunodeficiency virus (SIVmac) external envelope protein. The present study reports identification of five additional linear epitopes of SIVmac (isolate 251) by immunological screening of a peptide library expressed in yeast, using SIVmac-infected macaque sera. Three epitopes were localized in the envelope glycoproteins and the two others in the reverse transcriptase and in the Rev regulatory protein. Antibody response against the four envelope epitopes was monitored for 2 years in 12 macaques experimentally infected by SIVmac251. These four envelope regions represent major immunodominant epitopes of the SIVmac. Two epitopes are located in the V3 domain (a.a. 311-330) of the external gp130 and near the amino terminal part (a.a. 601-619) of the transmembrane gp36, in regions similar to those identified in HIVs, demonstrating immunological similarities between the envelopes of SIVs and HIVs. SIV-specific immunodominant epitopes were also identified in the V1 (a.a. 111-130) and V2 (a.a. 171-190) domains of the external gp130. In particular, antibody response against the V2 neutralizing region seems to play some role in the control of disease progression in SIVmac-infected macaques.

Amino Acid Sequence↗
PubMed1994

Chimeric hepatitis B core antigen particles containing B- and Th-epitopes of human papillomavirus type 16 E7 protein induce specific antibody and T-helper responses in immunised mice.

The use of hepatitis B core antigen (HBcAg) as an immunogenic delivery vehicle for foreign epitopes has been reported. Here we report the insertion of DNA sequences encoding immunodominant linear B-epitopes and a "universal" T-helper epitope of human papillomavirus (HPV) type 16 E7 transforming protein into the full-length HBcAg gene cloned into an inducible bacterial expression plasmid (pPN1.0). The resulting chimeric proteins assembled into particles which were highly immunogenic. Mice immunised with particles containing one or two of the three E7 B-epitopes under consideration produced strong epitope-specific antibody responses with both IgG and IgG2a components which recognised eukaryotic E7. T-proliferative responses were elicited to the E7 T-epitope as well as HBcAg T-epitope(s). Lymph node cells from immunised mice produced IL-2 and IL-4 when specifically recalled in vitro, indicating stimulation of both Th1 and Th2 helper cell compartments. Since HBcAg particles can be administered in adjuvant acceptable for human application and can elicit mucosal responses after nasal or oral immunisation, these results have implications for vaccine design in HPV 16-associated anogenital cancer.

Amino Acid Sequence↗
PubMed1994

Epitope detection in the envelope of intracellular naked orthopox viruses and identification of encoding genes.

Monoclonal antibodies (MAbs) were generated against vaccinia virus, cowpox virus KR2 Brighton, monkeypox virus Copenhagen, or ectromelia virus. Pairwise epitope specificity studies by competition ELISAs identified 23 distinct antigenic sites in 19 different orthopox virus strains. Six epitopes were completely independent of each other, and 17 closely related antigenic sites formed three separate epitope complexes. As shown by immunogold electron microscopy (ELMI), all MAbs reacted with epitopes in the envelope of intracellular naked virus, 16 MAbs recognized proteins of 32, 30, 16 or 14 kDa in Western blotting (WB), and 9 MAbs neutralized virus infectivity. In rabbitpox virus (RPV) 18 epitopes were detected. A lambda gt11 expression library of RPV DNA was screened with the corresponding 18 MAbs. Fourteen recombinant bacteriophage clones (ph) were isolated. Cross-hybridizations of phage and RPV DNA demonstrated a reaction with the HindIII A, HindIII D, or HindIII H fragments, respectively. DNA of ph3D was related to the A25L gene, which corresponds to the A-type inclusion body gene of cowpox virus. Two phage clones contained sequences of the 14-kDa fusion protein gene (A27L gene). Ph1A contained nearly the entire 14-kDa gene encoding 4 neutralizing (neutr) and 2 nonneutr epitopes. Ph5, expressing only half of this gene product, encoded 1 nonneutr epitope. The fusion protein of vaccinia virus MVA was isolated by immune-affinity chromatography with a neutr. catching MAb. The protein formed hollow rods (ELMI) and the 6 antigenic sites that were present were identical to those expressed by Escherichia coli infected with ph1A. WB detection with a polyclonal hyperimmune serum detected protein bands of 54, 32, 30, 16, and 14 kDa. The catching MAb bound only to a 16-kDa band. The purified fusion protein induced neutralizing antibodies in mice and rabbits.

Animals↗
PubMed2001

The conformational epitope of type III group B Streptococcus capsular polysaccharide.

In order to further characterize the conformational epitope of GBSPIII, we synthesized various oligosaccharides with the GBSPIII-related structures by a tailor-assembly synthetic scheme and a more traditional block-wise chemo-enzymatic approach. The oligosaccharides were used to probe the conformational epitope of GBSPIII using number of complementary techniques. The protective epitope of GPSPIII was further defined as length-dependent and conformational. The results of the studies confirmed that two repeating units (2RU) is the minimum binding unit and the epitope optimization mainly takes place between chain length 2RU to 7RU. Epitope optimization and multivalency were observed between 7RU and 20RU. The data support our hypothesis that the conformational epitope is an extended helical segment of the GBSPIII. GBSPIII exists mainly in the random coil form, which structurally mimics short oligosaccharide self-antigens, but it can infrequently and spontaneously form extended helices. Although not prevalent in GBSPIII the immune system preferentially selects these helical epitopes because they are unique to the polysaccharide.

Animals↗
PubMed1990

Multiple epitope specificity of monoclonal antibodies to a single synthetic peptide: use in the characterization of the GP IIb-IIIa binding domain of von Willebrand factor.

Monoclonal antibodies have been induced against the synthetic peptide with sequence Tyr-Glu-Val-Val-Thr-Gly-Ser-Pro-Arg-Gly-Asp-Ser-Gln-Ser-Ser. This peptide represents residues Glu1737-Ser1750 of the mature von Willebrand factor (vWF) subunit and contains the sequence Arg-Gly-Asp, thought to be important in mediating binding to the platelet receptor glycoprotein (GP) IIb-IIIa complex. Twelve antibodies were obtained, eight of which bound to native vWF as well as to the peptide immunogen insolubilized onto agarose beads. These antibodies defined at least three distinct epitopes, as demonstrated by antibody interaction with peptides having a single phenylalanine substitution at each position in the sequence. In particular, two antibodies bound to epitopes on vWF that included one or more of the three residues (arginine, glycine, aspartic acid) thought to be involved in binding to GP IIb-IIIa, whereas one antibody bound to an epitope that did not include any of those residues. Nevertheless, the three antibodies cross-reacted with each other, a finding explained by the fact that the corresponding epitopes had at least two residues in common, namely Gly1741 and Ser1742. In spite of the cross-reactivity for binding to vWF, only the two antibodies whose epitopes included residues in the Arg-Gly-Asp sequence inhibited vWF interaction with GP IIb-IIIa. The third antibody had no inhibitory effect even though it was bound to an epitope located at a distance of only few residues on the amino terminal side of Arg-Gly-Asp. These results demonstrate that monoclonal antibodies raised against a single synthetic peptide with sequence limited to fifteen residues may exhibit distinct epitope specificity and may be used to define functional domains in macromolecules with a high degree of resolution.

Amino Acid Sequence↗
PubMed1993

Assembly-dependent expression of antigenic epitopes by beta 2-microglobulin(b).

In this report we provide evidence for the expression of antigenic epitopes on mouse beta 2-microglobulin(b) (beta 2mb) that result from assembly with cognate H-2 class I heavy chains. For the cell line 69.9.15 (beta 2ma x beta 2mb), which expresses a mutant cytosolic form of H-2Kb and wild-type H-2Db, flow cytometry with rabbit antiserum against mouse beta 2m displayed beta 2m expression by cells grown in the presence or absence of fetal calf serum. By contrast, the epitopes identified by the beta 2mb-specific monoclonal antibody (mAb) S19.8 and clone 23 were not expressed by 69.9.15 cells grown in serum-containing conditions, and although S19.8 reactivity was weakly recovered by culture in the absence of serum, no such reactivity was observed with clone 23. Strong expression of these epitopes was achieved following transfection of 69.9.15 cells with the wild-type H-2Kb gene, indicating that the beta 2mb epitopes defined by mAb S19.8 and clone 23 were expressed when beta 2mb was assembled with an appropriate heavy chain. In support of this conclusion, we observed the recovery of the S19.8 and clone 23 epitopes by in vitro assembly of H-2Kb heavy chains with beta 2mb in the presence of the VSV N protein p52-59; however, such epitopes were expressed neither by beta 2mb prior to heterodimer assembly nor by non-conformed beta 2mb present in tissue culture supernatants recovered from H-2 class I surface positive cells. Taken together, these data indicate that in addition to the property of beta 2m to modify the antigenicity of the MHC class I heavy chains, beta 2m epitopes are induced in a reciprocal manner by assembly with MHC class I heavy chain molecules.

Animals↗
PubMed1991

Operational overlapping of cross-reactive and serotype-specific neutralization epitopes on VP7 of human rotavirus serotype 3.

VP7-specific neutralizing monoclonal antibodies (N-MAbs) to serotype 3 human rotavirus were produced to analyze serotype 3-specific and cross-reactive neutralization epitopes on VP7. On the basis of the reactivity patterns in neutralization tests with various human and animal strains, a total of 10 N-MAbs could be classified into four groups; five antibodies specific to serotype 3 were divided into two groups, and five antibodies consisted of two groups which are cross-reactive with strain 69 M (serotype 8) or strain WI61 (serotype 9). Seven N-MAbs showed the same reactivity patterns to the virus strains in both neutralization tests and enzyme-linked immunosorbent assay (ELISA), while three N-MAbs specific to serotype 3 in neutralization showed a cross-reactivity with the serotype 8 strain in ELISA. Neutralization-resistant mutants of serotype 3 strains P and YO were selected by the N-MAbs. Cross-neutralization tests between the mutants and the MAbs indicated the presence of two serotype-specific (S1 and S2) and three cross-reactive (C1, C2, and C3) epitope groups. S1, S2, and C3 epitope groups overlapped operationally each other, and the S1 epitope group had an overlapping with the C1 epitope group. However, C2 epitope group identified by the MAbs which neutralized serotypes 3 and 9, had no operational overlapping with any other epitope groups.

Animals↗
PubMed1989

Relative positions of some epitopes on carcinoembryonic antigen.

To investigate whether anti-(carcinoembryonic antigen) monoclonal antibodies (mAb) react with single or repeated epitopes, sandwich radioimmunoassays in homologous and heterologous combinations were performed. Four mAb (I-27, I-47, II-17 and to some degree II-16) gave homologous binding while two mAb (I-38S1 and II-10) did not. Taken together with previous immunoprecipitation studies we conclude that all these mAb except II-10 react with repeated epitopes. The relative positions of the epitopes recognized by these mAb and of three additional mAb (II-6, II-7 and CB-CEA-1) were investigated using a plate antibody competition test with enzyme-labelled carcinoembryonic antigen (CEA). mAb I-38S1, II-6, II-7, II-10, II-16 and CB-CEA-1 were mutually cross-reactive, and were classified as belonging to one epitope group. mAb I-27 and I-47 fell outside this group and did not interfere with the binding of CEA conjugate to mAb II-17 either. They therefore represent a second epitope group. mAb II-17 showed no interference with the binding of CEA to any of the other mAb and must therefore represent a third epitope group. The slopes of the plate antibody competition curves were used for calculation of a correlation matrix, which in turn was used to depict the relative positions of the epitopes recognized by the mAb in the large group.

Antibodies, Monoclonal↗
PubMed1998

Two dual-specific (anti-IgG and anti-dsDNA) monoclonal autoantibodies derived from the NZB/NZW F1 recognize an epitope in the hinge region.

The anti-IgG properties of two dual-specific (anti-dsDNA and anti-IgG) monoclonal NZB/NZW F1-derived autoantibodies, BV 17-45 and BV 16-13, were studied to resolve the location and possible commonality of the IgG epitope. To determine if BV 17-45 and BV 16-13 recognized the same IgG epitope, the relative temperature sensitivity of the conformational IgG epitopes were evaluated using the conformational sensitive immunoassay. Comparison of the temperature sensitivity of the conformational immunoglobulin epitopes over a temperature range of 25-100 degrees C suggested that the epitope recognized by BV 17-45 was the same as the IgG epitope recognized by BV 16-13. Further studies with papain- and pepsin-generated F(ab')2, Fab, and Fc fragments of BV 17-45 and BV 16-13 revealed that the dual-specific autoantibodies BV 17-45 and BV 16-13 both bound an epitope in the hinge region of the IgG molecule. The potential correlation between these studies and the pathogenic nature of dual-specific autoantibodies is discussed.

Animals↗
PubMed2000

A (1-->3,6)-beta-d-galactosyl epitope containing uronic acids associated with bioactive pectins occurs in discrete cell wall domains in hypocotyl and root tissues of flax seedlings.

We have used a well-characterized antibody specific for an epitope consisting of (1-->3,6)-beta-d-galactosyl residues with terminal glucuronic or 4-O-methylglucuronic acids of a bioactive pectin and immunocytochemistry to investigate its secretion and wall distribution in the hypocotyl and root tissues of flax seedlings. Our results show that this antigenic epitope is associated with flax pectins and is expressed by all the cells of the hypocotyl and root tissues. In the hypocotyl, it is abundant in the primary wall of epidermal cells as well as in the secondary wall of fiber cells, and is relatively less abundant in parenchyma cell walls. In contrast, the epitope is not detected in the middle lamellae and cell junction regions. In the root tip cells, immunogold electron microscopy shows that the cell walls of peripheral, columella, meristematic, cortical, and epidermal cells contain significant amounts of this epitope and that the distribution patterns are distinct. Together, these findings show that the antigenic epitope occurs in discrete domains of the wall implying a strict spatial regulation of the epitope-containing molecules. The results also show that, in root cells, the epitope is present within Golgi cisternae and is predominantly assembled in the trans and the trans-Golgi network compartments.

Antibodies↗
PubMed2003

A xylogalacturonan epitope is specifically associated with plant cell detachment.

A monoclonal antibody (LM8) was generated with specificity for xyloglacturonan (XGA) isolated from pea (Pisum sativum L.) testae. Characterization of the LM8 epitope indicates that it is a region of XGA that is highly substituted with xylose. Immunocytochemical analysis indicates that this epitope is restricted to loosely attached inner parenchyma cells at the inner face of the pea testa and does not occur in other cells of the testa. Elsewhere in the pea seedling, the LM8 epitope was found only in association with root cap cell development at the root apex. Furthermore, the LM8 epitope is specifically associated with root cap cells in a range of angiosperm species. In embryogenic carrot suspension cell cultures the epitope is abundant at the surface of cell walls of loosely attached cells in both induced and non-induced cultures. The LM8 epitope is the first cell wall epitope to be identified that is specifically associated with a plant cell separation process that results in complete cell detachment.

Antibodies, Monoclonal↗
PubMed2000

Cross-reactive and major virus-specific epitopes are located at the N-terminal halves of the cylindrical inclusion proteins of turnip mosaic and zucchini yellow mosaic potyviruses.

To investigate the antigenic nature of cylindrical inclusion proteins (CIPs) of the potyviruses Turnip mosaic virus (TuMV) and Zucchini yellow mosaic virus (ZYMV), monoclonal antibodies (MAbs) against the two CIPs were produced and epitopes on the CIPs were localized using Escherichia coli-expressed CIP fragments in Western blot analysis. All 23 MAbs against ZYMV CIP reacted only with ZYMV CIP. In contrast out of the 18 MAbs produced against TuMV CIP, 14 MAbs were TuMV CIP-specific while the remaining four MAbs cross-reacted with both CIPs. The four cross-reactive MAbs recognized two distinct epitopes in the N-terminal half of TuMV CIP corresponding to amino acid residues 103-119 and 224-237. Thirteen out of 14 TuMV CIP-specific MAbs recognized two distinct epitopes within residues 1-102 and 120-214, while the other one recognized an epitope within residues 301-644. On the other hand, 21 out of 23 ZYMV CIP-specific MAbs recognized epitopes within residues 1-118, while the remaining two recognized epitopes within residues 301-522. These results suggest that cross-reactive and major virus-specific epitopes are located at the N-terminal half of the respective CIPs.

Amino Acid Sequence↗
PubMed1984

Interspecies cross-reactivity of monoclonal antibodies to various epitopes of human plasminogen.

The immunological cross-reactivities of three conformationally specific monoclonal antibodies to distinct epitopes on human plasminogen toward plasminogens purified from 14 additional species have been examined. Antibody 10-F-1, which is produced against an epitope on the kringle 4 region of human plasminogen, shows a high degree (greater than 80%) of cross-reactivity against baboon, goat, monkey, ovine, and rabbit plasminogens; more limited (20-50%) cross-reactivity against bovine, equine, goose, guinea pig, mouse, rat, and porcine plasminogens; and little comparable cross-reactivity against canine and chicken plasminogens. Antibody 10-H-2, generated to an epitope of the kringles 1-3 region of human plasminogen, shows extensive cross-reactivity (72%) only toward monkey plasminogen, more limited (22-35%) cross-reactivity toward equine and rabbit plasminogens, and much less cross-reactivity toward any other of the above plasminogens. Antibody 10-V-1, also produced against an epitope on the kringle 1-3 region of human plasminogen, which is distinct from the 10-H-2 epitope, shows extensive cross-reactivity (72-100%) with baboon, monkey, and rabbit plasminogens; more limited cross-reactivity with equine (48%) and mouse (28%) plasminogens; and a low level of such reactivity with the remaining plasminogens. These studies show that the extent of interspecies cross-reactivity of various plasminogens greatly depends upon the epitope in question. The K4 region of these molecules appears more extensively conserved than the K1-3 region, at least in regard to the particular epitopes examined in this study.

Animals↗
PubMed1991

Disposition of mitochondrially bound hexokinase at the membrane surface, deduced from reactivity with monoclonal antibodies recognizing epitopes of defined location.

A panel of monoclonal antibodies against rat brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) has been employed to investigate the orientation of the mitochondrially bound enzyme on the mitochondrial surface. Based on their ability to immunoprecipitate truncated forms of the protein, obtained by in vitro translation of truncated versions of the mRNA, the epitopes for seven monoclonal antibodies were mapped to regions consisting of 20-50 amino acid residues within the sequence of the N-terminal half of the enzyme. There is extensive sequence similarity between the N- and C-terminal halves of this enzyme, which is thought to have evolved by a process of gene duplication and fusion. However, these antibodies react selectively with epitopes in the N-terminal half, and thus epitopic regions for several of these antibodies could be further defined by eliminating from consideration regions showing substantial sequence similarity with the C-terminal half. The epitope for one of the monoclonal antibodies, designated 4D4, was shown to involve the extreme N-terminus of the enzyme; selective proteolytic modification of this region resulted in loss of immunoreactivity. Relative location of epitopes for three other antibodies, designated 2B, 1C5, and 4C5, within a 20-residue segment was deduced from effects of modifying sulfhydryl residues within this segment on immunoreactivity. Thus, by a combination of sequence analysis and experimental methods, the epitopes for these seven antibodies could be localized to defined regions within the overall sequence. The ability of these antibodies to prevent binding of hexokinase to mitochondria, and their ability to recognize the mitochondrially bound enzyme, provided a basis for assessing the relative proximity of the corresponding epitopes to the mitochondrial surface when the enzyme was bound. The disposition of the bound enzyme on the mitochondrial surface was deduced by relating these results to the proposed structure for brain hexokinase.

Amino Acid Sequence↗
PubMed1991

Epitope mapping of the receptor-bound agonistic form of human chorionic gonadotropin (hCG) in comparison to the antagonistic form (deglycosylated hCG).

On the surface of free human chorionic gonadotropin (hCG), we can distinguish with our panel of monoclonal antibodies (MCA) 14 topographically distinct epitopes (designated alpha 1 - alpha 5, beta 1 - beta 5, alpha beta 1 - alpha beta 4, depending on the subunit they are attached to). Only 2, i.e. the adjacent beta 3 and beta 5 epitopes, of these 14 are accessible to 125I-labeled MCA binding, when hCG is first allowed to bind to the rat testis hCG receptor. This result indicates that the agonist hCG assumes a defined orientation in its receptor-bound state and that, except for that small area comprising the beta 3 and beta 5 epitopes, most of its surface is masked by the hCG receptor. We therefore asked whether the competitive antagonist deglycosylated hCG (degly-hCG), which, when free, is antigenically (as to number and topography of epitopes) indistinguishable from native hCG, would interact with the receptor differently, that is, in a way that can be discerned by this epitope accessibility paradigm. Here we describe that on receptor-bound degly-hCG the beta 3 and beta 5 epitopes were concealed as were all other epitopes. This observation, together with finding the receptor affinity of degly-hCG to be 4 times higher than that of native hCG, suggests that degly-hCG assumes a signal transduction-incompetent ligand orientation and at the same time interacts with the receptor more intensively, i.e. establishes additional ("antagonist accessory") protein-protein contacts besides those involved in agonist binding. It thus appears that the carbohydrate moieties function to prevent formation of such accessory contacts.

Animals↗