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

Abstract

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.

Sialic acid and sialyl‐lactose glyco‐conjugates: design, synthesis and binding assays to lectins and swine influenza H1N1 virus

“…Sequential oligopeptide carriers (SOCn, n = 2–7), a novel foldamer class of artificial carriers, was introduced by our laboratory as a tool for the construction of reconstituted protein mimics with various functionalities . Here, the terminal parts, sialic acid and sialyllactose, of the HA receptor, critical for the recognition of the influenza virus, were linked independently to SOC 4 to reconstitute mimics of the receptor.…”

“…SOC 4 is a sterically constrained scaffold comprising α ‐aminoisobutyric acid (Aib), a strongly helicogenic C α ‐tetrasubstituted amino acid. It was found that the beneficial structural elements of SOC 4 (helical conformation), attributed mainly to the inclusion of Aib, induce a favorable arrangement of the conjugated biomolecules, which retain their initial ‘active’ conformation and their potential for site‐specific interactions . Sialic acid, 3′‐sialyllactose and 6′‐sialyllactose, which are the terminal and most critical parts of the HA receptor for its recognition of influenza viruses, were coupled to SOC 4 to formulate simplified reconstituted mimics of the receptors.…”

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

“…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). …”

Nanomaterials, Autophagy, and Lupus Disease

“…MAPs were also used to present the DWEYS peptide for testing cross‐reacting dsDNA antibodies in the context of neuropsychiatric lupus and for animal immunizations . Examples of constructions with SOC include peptides of the La/SSB antigen, the motif PPGMRPP present in several RNPs, and peptides of the α‐subunit of the Torpedo nicotinic acetylcholine receptor, a target of autoantibodies from patients with myasthenia gravis . Along this direction, we recently developed a molecular system based on adamantane dendrons (Figure ).…”