Complementary Peptide Epitopes and Antiidiotypic Antibodies in Autoimmunity

Sakarellos‐Daitsiotis, Maria; Cung, Manh Thông; Sakarellos, Constantinos; Hilali, Zouhair El; Kosmopoulou, Aggeliki; Voitharou, Chryssa

doi:10.2174/0929866043407020

Cited by 5 publications

(4 citation statements)

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“…In a Lewis rat model of MS (experimental autoimmune encephalomyelitis (EAE)), inverse hydropathy peptide administration and the subsequent anti-Id response reduced severity of disease, and frequency of relapse (64). Finally, there have been recent studies showing the effectiveness of a complementary peptide to La/SSB, the main auto-antigen in both systemic lupus erythematosus and Sjogren’s syndrome (4, 65). …”

Section: Design Of Future Therapeuticsmentioning

confidence: 99%

“…Autoimmunity is a condition that has been reported to afflict 1 in 31 people in the United States alone (1). While there are low level amounts of self-reactive T cells and auto-Abs detected in the healthy population, they are held in check by a system of regulatory T cells (T reg ) and both Id and anti-Id Abs (2–4). It is when there is a dysregulation of this system of T reg cells and Abs that autoimmunity occurs.…”

Section: Introductionmentioning

confidence: 99%

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Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity

Hardison

Blalock²

2012

Front Biosci

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Perhaps behind only the understanding of the genetic code in importance is the comprehension of protein sequence and structure in its effect on modern scientific investigation. How proteins are structured and interact dictates a considerable amount of the body’s processes in maintaining homeostasis. Unfortunately, in diseases of autoimmunity, these processes are directed against the body itself and most of the current clinical responses are severely lacking. This review addresses current therapeutics involved in the treatment of various autoimmune diseases and details potential future therapeutics designed with a more targeted approach. Detailed in this manuscript is the concept of utilizing peptides possessing an inverse hydropathy to the immunogenic region of proteins to generate anti-idiotypic (anti-Id) and anti-clonotypic T cell receptor (TCR) antibodies (Abs). Theoretically, the anti-Id Abs cross react with Id Abs and negate the powerful machinery of the adaptive immune response with little to no side effects. A series of studies by a number of groups have shown this to be an exciting and intriguing concept that will likely play a role in the future treatment of autoimmune diseases.

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Section: Design Of Future Therapeuticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity

Hardison

Blalock²

2012

Front Biosci

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“…Autoimmunity is a condition that has been reported to afflict 1 in 31 people in the United States alone (1). While there are low level amounts of self-reactive T cells and auto-Abs detected in the healthy population, they are held in check by a system of regulatory T cells (T reg ) and both Id and anti-Id Abs (2)(3)(4). It is when there is a dysregulation of this system of T reg cells and Abs that autoimmunity occurs.…”

Section: Introductionmentioning

confidence: 99%

Molecular recognition theory and sense-antisense interaction therapeutic applications in autoimmunity

Blalock¹

2012

Front Biosci

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Perhaps behind only the understanding of the genetic code in importance is the comprehension of protein sequence and structure in its effect on modern scientific investigation. How proteins are structured and interact dictates a considerable amount of the body's processes in maintaining homeostasis. Unfortunately, in diseases of autoimmunity, these processes are directed against the body itself and most of the current clinical responses are severely lacking. This review addresses current therapeutics involved in the treatment of various autoimmune diseases and details potential future therapeutics designed with a more targeted approach. Detailed in this manuscript is the concept of utilizing peptides possessing an inverse hydropathy to the immunogenic region of proteins to generate anti-idiotypic (anti-Id) and anti-clonotypic T cell receptor (TCR) antibodies (Abs). Theoretically, the anti-Id Abs cross react with Id Abs and negate the powerful machinery of the adaptive immune response with little to no side effects. A series of studies by a number of groups have shown this to be an exciting and intriguing concept that will likely play a role in the future treatment of autoimmune diseases.

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“…The most prominent finding emerging from this study was the unmasking of the anti-La/SSB response, in sera from patients with pSS and SLE, by specific blocking of the anti-Id antibodies using the complementary cpep349-364 of the La/SSB epitope pep349-364 [25]. Id/anti-Id circuit, as well as T cell proliferative response was also observed in mice immunized with La/SSB epitopes and their counterparts [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

A complementary La/SSB epitope anchored to Sequential Oligopeptide Carrier regulates the anti‐La/SSB response in immunized animals

Voitharou

Krikorian

Sakarellos

et al. 2008

Journal of Peptide Science

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Complementary peptide epitopes, derived from complementary RNA sequences, have been used for suppressing the autoimmune response in experimental autoimmune diseases as myasthenia gravis, allergic neuritis and allergic encephalomyelitis. Aiming at contributing to the development of a tool that could regulate the autoantibody production against La/SSB, which is the main target of autoantibodies in Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE), the complementary epitope, cpep349-364, of the minor T/major B cell epitope of La/SSB, pep349-364, was utilized for the induction of neutralizing anti-cpep349-364 antibodies in rabbit immunizations. Complementary peptides were coupled to an artificial carrier, developed in our laboratory, in order to enhance the complementary potency of cpep349-364 and its counterpart. This carrier, named Sequential Oligopeptide Carrier, SOC(n), formed by the repeating tripeptide Lys-Aib-Gly, adopts helical conformation, which allows the anchored peptide epitopes to preserve their initial reactivity such as molecular recognition, antigenicity/immunogenicity. Our study provides proof of evidence of specific interactions between idiotypic (Id)/anti-idiotypic (anti-Id) antibodies generated in immunized animals by the sense epitope (conjugate I) of La/SSB and its complementary counterpart (conjugate II). It was also demonstrated that the Id/anti-Id association is specifically disrupted by adding either the sense epitope (conjugate I) or its complementary counterpart (conjugate II). A mutual neutralization of Id/anti-Id antibodies was observed in vivo, which implies that generation of anti-Id antibodies by immunization with the complementary La/SSB epitope could scavenge the anti-La/SSB response.

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Complementary Peptide Epitopes and Antiidiotypic Antibodies in Autoimmunity

Cited by 5 publications

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Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity

Molecular recognition theory and sense-antisense interaction: therapeutic applications in autoimmunity

Molecular recognition theory and sense-antisense interaction therapeutic applications in autoimmunity

A complementary La/SSB epitope anchored to Sequential Oligopeptide Carrier regulates the anti‐La/SSB response in immunized animals

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