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

Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA.
Mol Aspects Med 1992
PMID:HLA and disease. 128 96

Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable degree of molecular mimicry to the extracellular matrix protein elastin. It contains both repetitive motifs PGVGV and VGVAPG. Immunofluorescence using a monoclonal antibody against VGVAPG confirmed that this peptide is expressed on sporozoites as predicted. The presence of VGVAPG is particularly interesting since this is the ligand for elastin receptors on a range of cell types, including macrophages/monocytes which are a major class of host target cells. It is proposed that this antigen represents the ligand whereby T. annulata recognises its host cells.
Mol Biochem Parasitol 1992 Jul
PMID:Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen. 150 30

In order to study the structural and functional mimicry of an antigen by anti-idiotypic antibodies, we generated anti-idiotopic monoclonal antibodies (anti-Id mAbs) against a mAb (R45-45-11) with specificity for the immunosuppressive cyclic undecapeptide cyclosporine (Cs; Sandimmune). Three out of five anti-Id mAbs inhibited the binding of Cs to the anti-Cs mAb R45-45-11. All anti-Id mAbs cross-reacted only with one (anti-Cs mAb V45-271-10) out of 19 anti-Cs mAbs. The anti-Cs mAb V45-271-10 recognizes an epitope on the Cs molecule which is very similar to that recognized by R45-45-11. R45-45-11 and V45-271-10 differ only by one amino acid in the variable region. The anti-Id mAbs which recognize combining site-associated idiotopes (Ids) reverse the blocking effect of the anti-Cs mAb R45-45-11 on Cs immunosuppression in vitro. The sequences of the variable regions of heavy and light chain of one anti-Id mAb were determined. X-ray analysis of the corresponding Fab fragment, either alone or complexed with the Fab fragment of the Id, is currently in progress.
Mol Immunol 1992 Mar
PMID:Anti-cyclosporine monoclonal antibodies and their anti-idiotopic counterpart: structure and biological activity. 155 45

Molecular mimicry has been considered as a possible way for parasites to escape host immune responses. This work concerns the characterization of protein determinants shared by Schistosoma mansoni and its intermediate host Biomphalaria glabrata. Parasite (Sm39) and mollusc (Bg 39) cross-reactive proteins were identified and shown to induce in rabbit and mouse, antibodies specific for invertebrate determinants. Ultrastructural studies demonstrated that antibodies to Sm39 specifically bound to muscular structures of parasite and mollusc. Molecular cloning and sequencing indicated that Bg39 corresponded to a muscular isoform of tropomyosin. The mollusc sequence showed a 51-65% homology with seven different muscular tropomyosins from vertebrate and invertebrate species. The highest score of homology was observed with S. mansoni tropomyosin, suggesting that cross-reactive determinants could be specific for the trematode and its intermediate host. In miracidia, Sm39 epitopes were also shown to be contained in the vesicles present in epidermal ridges and cellular bodies. Such vesicles are involved in the formation of a protective tegument around sporocysts, suggesting a possible role of cross-reactive tropomyosins in miracidia and/or sporocyst-snail interactions.
Mol Biochem Parasitol 1990 Dec
PMID:Structural homology of tropomyosins from the human trematode Schistosoma mansoni and its intermediate host Biomphalaria glabrata. 209 Sep 46

The beta-turn, which has also been referred to as the beta-bend, beta-loop or reverse turn, has been implicated as an important site for molecular recognition in many biologically active peptides and in globular proteins. This small secondary structure therefore makes an attractive target for mimicry by a conformational constraint, because a peptide which is constrained in a biologically active conformation can display a number of advantages over the parent substrate. The less peptide-like such a constraint is, the more potential there is to maximize these advantages. A decade has passed since the first (and highly successful) attempt to mimic the beta-turn with a nonpeptide conformational constraint was disclosed by Freidinger et al. (1980). Since this report, rapidly growing interest in the field of nonpeptide beta-turn mimics has seen a variety of experimental approaches and a mixed bag of results. It is attempted in this review, not only to summarize and critically analyse these approaches, but also to touch on the complexities associated with the conformational mimicry of such a diverse structure as the beta-turn.
J Mol Recognit 1990 Apr
PMID:Conformational constraints: nonpeptide beta-turn mimics. 216 68

No cross-reaction could be detected between purified myelin basic proteins (MBP) from mouse, rat or human origins and envelope proteins of viruses suspected of inducing demyelinating processes. In the experimental model using Theiler's murine encephalomyelitis virus, competition radioimmunoassay failed to detect any cross-reaction between MBP and VP1, VP2 and VP3 envelope antigens. In the human situation, antibodies against SV5 and measles viruses, both etiologically linked with multiple sclerosis, also failed to recognize MBP. These results rule out molecular mimicry as a cause of demyelination.
Mol Immunol 1989 Jul
PMID:Lack of cross-reaction between myelin basic proteins and putative demyelinating virus envelope proteins. 247 71

The development of a non-competitive, solid-phase radioimmunoassay for quantitating anti-actin antibody is described. Anti-actin antibody was captured on BSA-coated microspheres of polystyrene to which a synthetic peptide representing the fifteen amino acid N-terminus of human beta-actin was covalently attached. A rabbit antiserum against the actin peptide fragment was used as reference serum for the assay. Serums of 23 out of 28 (82%) patients with chronic active hepatitis, shown to have anti-actin antibodies (range 2-140 micrograms ml-1) by immunofluorescence and immunoblot assays, were used to validate the radioimmunoassay. Only 7 out of 130 (5%) control subjects exhibited anti-actin antibody serum concentrations above 14 micrograms ml-1 (range 2-20 micrograms ml-1), the 95% confidence interval. Anti-actin antibody serum concentrations were determined to be elevated in 28 out of 47 (60%) patients with juvenile rheumatoid arthritis (range 5-89 micrograms ml-1), 43 out of 64 (67%) patients with human immunodeficiency virus infection and AIDS (range 3-80 micrograms ml-1), and 17 out of 23 (74%) infants with Kawasaki Syndrome (range 7-138 micrograms ml-1). All of the differences observed between patient groups, either singly or collectively, and the control group are highly significant (P less than 0.001) as judged by chi-square analysis. Since all of these disease states contain elements of viral infection and autoimmune disease, it is possible that viral infection in these diseases triggers the production of anti-actin antibody, possibly by means of molecular mimicry in response to viral oncogenes or to abnormal expression of actin in host tissue. This radioimmunoassay for anti-actin antibodies may prove to be a useful tool for the detection and monitoring of certain forms of autoimmune disease.
Mol Cell Probes 1988 Dec
PMID:Radioimmunoassay for anti-actin antibody: application in viral and autoimmune diseases. 307 13

In order to design and produce effective vaccines based upon the idiotype network hypothesis of Jerne, a thorough understanding of the biological and structural aspects underlying the stimulating activities of anti-idiotypic antibodies is needed. Here we determined the nucleotide sequence of the variable heavy and light chain regions of two monoclonal anti-idiotypic antibodies which induce different anti-phosphorylcholine responses. The nucleotide sequences of the variable domains of two monoclonal anti-TEPC 15 (T15) antibodies (F6-3 and 4C11) were determined by the primer extension and Maxam-Gilbert techniques. The nucleotide sequence data show that 4C11 and F6-3 have homologous VH segments and JH segments, but different D regions. The VH segments of both clones belongs to the J558 VH family. Most of the differences among the VH segments are located in CDR2. The VK segments of 4C11 and F6-3 are homologous to the VK gene group 4 and group 8, respectively. Comparison of the sequences of 4C11 and F6-3 with other published anti-idiotype antibodies shows that there is no preferential utilization of immunoglobulin genes. An analysis of the distribution of charged residues and hydropathic comparison studies were used to interpret the sequence of 4C11 in terms of the biological mimicry of antigenic stimulation.
Mol Immunol 1988 Jan
PMID:Structural basis of stimulatory anti-idiotypic antibodies. 312 24

We have analysed the structure of the Xenopus beta globin gene 5' flanking region in erythroid and non-erythroid chromatin, in supercoiled plasmids and in minichromosomes assembled in HeLa cell transfections. We have identified two erythroid chromatin-specific, nuclease-hypersensitive sites (HSs), one centred on the cap site, the other located 1000 base-pairs further upstream. An (AT)n tract is located 200 base-pairs upstream from each of these sites. In supercoiled plasmids, the (AT)n tracts, and not the chromatin HSs, are preferentially cleaved by single strand and double strand-specific nucleases. Using restriction enzymes, we have looked at the structure of the cap site HS in minichromosomes assembled in HeLa cell transfections. We find that the structure is indistinguishable from that found in erythroid chromatin, thus reinforcing our previous suggestion, based only on DNase I studies, that the formation of this HS is not dependent on erythroid-specific factors. In view of this close structural mimicry of the situation in vivo, we have used the HeLa cell model system to study the sequences required for cap site HS formation. We find that deletion of the (AT)n tract immediately upstream influenced neither the formation of the HS nor transcription of the globin gene. Indeed, these features remained unaffected by further deletion of upstream sequences, including 50 base-pairs of the HS itself. In this construct, the dimensions of the HS remained the same as in the undeleted construct, with the plasmid sequences that replaced the deleted Xenopus sequences becoming hypersensitive. Thus, HS formation is directed by sequences downstream from --116 acting over a distance of at least 50 base-pairs.
J Mol Biol 1988 Feb 20
PMID:5' structural motifs and Xenopus beta globin gene activation. 335 44

The gene V protein of the filamentous bacteriophages fl, fd and M13, and the gene 32 protein of bacteriophage T4 share the property of binding strongly and co-operatively to single-stranded nucleic acids, especially DNA. Moreover, both are capable of repressing the translation of specific mRNAs (gene 32 protein its own, and gene V protein that of the filamentous phage gene II), both in vivo and in vitro. If the mechanism of repression by either of these proteins were based solely on its ability to bind single strands co-operatively, then the other would be expected to mimic or interfere with its effect in vitro. We have found no such mimicry or interference, even at protein concentrations high enough to have substantial non-specific effects on translation. This suggests that the sites of repression on the mRNAs must offer something other than simple "unstructuredness" for binding and repression to occur.
J Mol Biol 1984 Feb 25
PMID:Specificity of translational regulation by two DNA-binding proteins. 660 87


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