Role of complementary proteins in autoimmunity: an old idea re-emerges with new twists

McGuire, Kathleen L.; Holmes, David S.

doi:10.1016/j.it.2005.05.001

Cited by 30 publications

(39 citation statements)

References 49 publications

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“…Antisense peptide design is closely related to the genetic code structure [1,2,3,4,5,6]. Sixty-four codons of the genetic code consist of three nucleotide bases.…”

Section: Resultsmentioning

confidence: 99%

“…In the last two decades antisense peptides became a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation [1,2,3,4,5,6,7]. They have been used in biomedicine for efficient modeling of more than 40 peptide–receptor systems [1,2,3,4,5,6,7].…”

Section: Introductionmentioning

confidence: 99%

“…They have been used in biomedicine for efficient modeling of more than 40 peptide–receptor systems [1,2,3,4,5,6,7]. …”

Section: Introductionmentioning

confidence: 99%

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A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

Štambuk

Manojlović

Turčić

et al. 2014

IJMS

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Antisense peptide technology is a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation. It is based on the fact that peptides specified by the complementary (antisense) nucleotide sequences often bind to each other with a higher specificity and efficacy. We tested the validity of this concept on the example of human erythropoietin, a well-characterized and pharmacologically relevant hematopoietic growth factor. The purpose of the work was to present and test simple and efficient three-step procedure for the design of an antisense peptide targeting receptor-binding site of human erythropoietin. Firstly, we selected the carboxyl-terminal receptor binding region of the molecule (epitope) as a template for the antisense peptide modeling; Secondly, we designed an antisense peptide using mRNA transcription of the epitope sequence in the 3'→5' direction and computational screening of potential paratope structures with BLAST; Thirdly, we evaluated sense–antisense (epitope–paratope) peptide binding and affinity by means of fluorescence spectroscopy and microscale thermophoresis. Both methods showed similar Kd values of 850 and 816 µM, respectively. The advantages of the methods were: fast screening with a small quantity of the sample needed, and measurements done within the range of physicochemical parameters resembling physiological conditions. Antisense peptides targeting specific erythropoietin region(s) could be used for the development of new immunochemical methods. Selected antisense peptides with optimal affinity are potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.

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“…Antisense peptide design is closely related to the genetic code structure [1,2,3,4,5,6]. Sixty-four codons of the genetic code consist of three nucleotide bases.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

Štambuk

Manojlović

Turčić

et al. 2014

IJMS

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“…A study of outstanding interest was conducted by Pendergraft et al [75] , who investigated the role of complementary proteins in WG. In brief, the amino acid sequence of a specific protein is generally coded by the 'sense' strand of DNA [76] . Transcribing and translating this information results in a 'sense' protein.…”

Section: Staphylococcus Aureus-induced Immune Alterations and Wgmentioning

confidence: 99%

“…The anti-sense strand carries genetic code of the complementary peptide that is the counterpart of the 'sense' protein [76] . Pendergraft et al [75] hypothesize that the initial immune response in autoimmunity is directed against complementary PR3 (cPR3), resulting in the formation of antibodies against cPR3 (idiotypic response).…”

Section: Staphylococcus Aureus-induced Immune Alterations and Wgmentioning

confidence: 99%

T-Lymphocytes and Disease Mechanisms in Wegener’s Granulomatosis

Fan¹,

Wilde²,

Dolff³

et al. 2009

Kidney Blood Press Res

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The mechanisms underlying Wegener’s granulomatosis (WG) are not well understood. The role of T-cells in the pathogenesis of WG has only recently come into focus of research. This review presents recent developments regarding the role of T-cells in WG. The occurrence of anti-neutrophil-cytoplasmic antibodies (ANCA) directed against proteinase-3 (PR-3) is a hallmark of WG. ANCA seem to mediate vasculitic damage in WG. Apart from ANCA, T-cells are involved in disease mechanisms. T-cells might participate in ANCA formation. Furthermore, T-cells are observed in affected tissue and granulomatous lesions. T-cells are indispensable for granuloma formation in other diseases and this might apply to WG too. In line with this, several aberrations of T-cell populations and alterations of the T-cell response were recently discovered in patients suffering from WG. Therefore, the impact of T-cell polarization, genotypic alterations modifying T-cell function and specific T-cell subsets on disease pathogenesis is discussed. Moreover, the influence of Staphylococcus aureus on T-cells and self-tolerance in WG is further elucidated. Finally, therapeutic options and implications with regard to T-cell-mediated pathogenesis are highlighted.

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Idiotype Network

Behn¹

2011

Encyclopedia of Life Sciences

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B‐lymphocytes have receptors, antibodies, with highly specific binding sites which bind to complementary structures. Receptors of a given cell have exactly one specific set of binding sites, the idiotype. Complementary structures can be found not only on antigen but also on antibodies of different idiotype or on T‐cell receptors. Thus a network of idiotypically interacting immune cells is formed, the idiotype network. The network influences the shaping of the B‐ and T‐cell repertoirs and may be relevant in the control of autoreactive clones. The therapeutic use of monoclonal antibodies against autoimmune diseases, cancer (in particular lymphoma) and a few other diseases relies on idiotypic interactions and is of rapidly growing importance. This strongly motivates further research to understand the systemic consequences of immunomanipulation. Key Concepts: An idiotope is a site on a B‐cell receptor that can bind to complementary structures; also on T‐cell receptors such sites exist. The collection of idiotopes on one receptor is called idiotype; all receptors of a given cell have the same specific idiotype. A huge diversity of idiotypes is generated by random somatic rearrangements of genes. B‐cells of a given idiotype are stimulated to proliferate if its receptors are cross‐linked by complementary structures; unstimulated cells die. Structures that bind to idiotopes can be found on antigen, not only on B or T cells of anti‐idiotype, but also on other cells or signalling molecules. Immune cells, functionally connected by idiotypic interactions, form the idiotype network which influences the shaping of the B‐ and T‐cell repertoir and may be relevant in the control of autoreactive clones. Therapeutic strategies using monoclonal antibodies rely on idiotypic interactions. New technologies make extensive studies of the repertoir of immune receptors feasable, which are necessary to better understand the network properties and systemic consequences of immunomanipulation. In many different fields the network paradigm has proved successful in describing complex systems, the recent progress in theoretical understanding should inspire further research on idiotype networks.

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Role of complementary proteins in autoimmunity: an old idea re-emerges with new twists

Cited by 30 publications

References 49 publications

A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

A Simple Three-Step Method for Design and Affinity Testing of New Antisense Peptides: An Example of Erythropoietin

T-Lymphocytes and Disease Mechanisms in Wegener’s Granulomatosis

Idiotype Network

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