Structural Basis for Antibody Recognition of Lipid A

Haji-Ghassemi, O.; Müller‐Loennies, Sven; Rodrı́guez, Teresa; Brade, Lore; Kosma, Paul; Brade, Helmut; Evans, Stephen V.

doi:10.1074/jbc.m115.657874

Cited by 11 publications

(7 citation statements)

References 63 publications

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“…It has been shown that anti-lipid A antibodies may cross-react with the lipid A of different species of bacteria, as well as with molecules present in humans, such as ssDNA, cardiolipin, or ligands on human B lymphocytes. It is believed that the cross-reactivity between lipid A and other host molecules may affect the development of autoimmune diseases [ 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus mirabilis O3 (S1959) Lipopolysaccharide May React with Collagen Type I

Durlik-Popińska

Żarnowiec

Lechowicz

et al. 2020

IJMS

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Most rheumatic diseases, including rheumatoid arthritis (RA), are characterized by immune disorders that affect antibody activity. In the present study, using Dot blot and ELISA assay, we showed that patients with rheumatic disease produced significantly more antibodies against lipopolysaccharide (LPS) P. mirabilis O3 compared to healthy donors (p < 0.05), and affinity purified antibodies against LPS O3 may cross-react with collagen type I. It was demonstrated that purified of antibodies isolated from RA patients sera, reacted stronger with the collagen than healthy donors (p = 0.015), and cross-reaction was correlated with level of anti-citrullinated peptide antibodies (r = 0.7, p = 0.003). Moreover, using six different lipopolysaccharides were demonstrated the significant correlations in sera reactivity among lysine-containing lipopolysaccharides observed in patients’ sera (p < 0.05). Using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR) it was shown that unique wavenumbers of sera spectra correlate with reactivity with lipopolysaccharides allowing distinguish patients from healthy blood donors. Antibodies adsorption by synthetic antigens shows that in patients’ group anti-LPS O3 antibodies can be adsorbed by both amides of galacturonic acid and lysine or threonine, which suggests less specificity of antibodies binding with non-carbohydrate LPS component. The observed correlations suggest that non-carbohydrate components of LPS may be an important epitope for less specific anti-LPS antibodies, which might lead to cross-reactions and affect disease development.

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Section: Discussionmentioning

confidence: 99%

Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus mirabilis O3 (S1959) Lipopolysaccharide May React with Collagen Type I

Durlik-Popińska

Żarnowiec

Lechowicz

et al. 2020

IJMS

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“…Thus, the presence of the V H 10 CDR2 loop seems to be critical for DNA binding in this experimental setup, corroborating the role for the CDR2 in V H 10 germline sequences. The importance of heavy chain CDR2 in antigen binding has been reported before [25,30].…”

Section: Discussionmentioning

confidence: 95%

“…All models showed a single-chain conventional VH-VL pairing. Compared to another pre-BCR structure in PDB (2H32), it showed a Sequence alignment of the V H 10 chain used in scpre-BCR with the two anti-DNA antibodies 1CBV [24], 4Z8F [25] shows that the V chain sequences are very similar and share the adjacent arginine residue at position 50 and 52 (Figure 6). Thus, a potential salt-bridge could be formed with DNA's phosphate groups, allowing the V H 10 germline chain the ability to bind DNA independently of CDR3 or the V L domain.…”

Section: A Structural Model Of Scprebcr-vh10 Supports Dna Intrinsic Binding For Dnamentioning

confidence: 99%

A Germline-Encoded Structural Arginine Trap Underlies the Anti-DNA Reactivity of a Murine V Gene Segment

Araújo

França

Valadares

et al. 2021

IJMS

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Autoimmunity may have its origins of early repertoire selection in developmental B cells. Such a primary repertoire is probably shaped by selecting B cells that can efficiently perform productive signaling, stimulated by self-antigens in the bone marrow, such as DNA. In support of that idea, we previously found a V segment from VH10 family that can form antibodies that bind to DNA independent of CDR3 usage. In this paper we designed four antibody fragments in a novel single-chain pre-BCR (scpre-BCR) format containing germinal V gene segments from families known to bind DNA (VH10) or not (VH4) connected to a murine surrogate light chain (SLC), lacking the highly charged unique region (UR), by a hydrophilic peptide linker. We also tested the influence of CDR2 on DNA reactivity by shuffling the CDR2 loop. The scpre-BCRs were expressed in bacteria. VH10 bearing scpre-BCR could bind DNA, while scpre-BCR carrying the VH4 segment did not. The CDR2 loop shuffling hampered VH10 reactivity while displaying a gain-of-function in the nonbinding VH4 germline. We modeled the binding sites demonstrating the conservation of a positivity charged pocket in the VH10 CDR2 as the possible cross-reactive structural element. We presented evidence of DNA reactivity hardwired in a V gene, suggesting a structural mechanism for innate autoreactivity. Therefore, while autoreactivity to DNA can lead to autoimmunity, efficiently signaling for B cell development is likely a trade-off mechanism leading to the selection of potentially autoreactive repertoires.

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“…Более того, на основе моноклональных антител к липиду А разработана иммунохимическая тест-система, позволяющая с удовлетворительной чувствительностью (10 5 клеток/ мл) выявлять бактерии Escherichia coli O157 [69]. Вместе с тем многочисленные исследования, направленные на разработку терапевтических средств на основе моноклональных антител к липиду А ряда грамотрицательных бактерий, к настоящему времени не завершились успешными клиническими испытаниями [26]. Будущие исследования должны показать, способны ли сами клетки патогенных иерсиний, а не только выделенный из них препарат ЛПС, связываться с эукариотической клеткой посредством липида А.…”

Section: небелковые адгезиныunclassified

Yersinia pseudotuberculosis-derived adhesins

Byvalov

Konyshev

2019

Russian Journal of Infection and Immunity

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Around fifteen surface components referred to adhesins have been identified in Yersinia pseudotuberculosis combining primarily microbiological, molecular and genetic, as well as immunochemical and biophysical methods. Y. pseudotuberculosis-derived adhesins vary in structure and chemical composition but they are mainly presented by protein molecules. Some of them were shown to participate not only in adhesive but in other pathogen-related physiological functions in the host-parasite interplay. Adhesins can mediate bacterial adhesion to eukaryotic cell either directly or via the extracellular matrix components. These adhesion molecules are encoded by chromosomal DNA excepting YadA protein which gene is located in the calcium-dependence plasmid pYV common for pathogenic yersisniae. An optimum temperature for adhesin biosynthesis is located close to the body temperature of warm-blooded animals; however, at low temperature only invasin InvA, full-length smooth lipopolysaccharide and porin OmpF are produced in Y. pseudotuberculosis. Several adhesins (Psa, InvA) can be expressed at low pH (corresponds to intracellular content), thereby defining pathogenic yersiniae as facultative intracellular parasites. Three human Yersinia genus pathogens differ by ability to produce adhesins. Y. pseudotuberculosis adherence to host cells or extracellular matrix components is determined by a cumulative adhesion-based activity, which expression depends on chemical composition and physicochemical environmental conditions. It’s proposed that at the initial stage of infectious process adherence of Y. pseudotuberculosis to intestinal epithelium is mediated by InvA protein and “smooth” LPS form. These adhesins are produced in bacterial cells at low (lower than 30°С) temperature occurring in environment from which a pathogen invades into the host. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, possibly, liver and spleen. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, perhaps, liver and spleen. Qualitative and quantitative spectrum of Y. pseudotuberculosis adhesins is determined by environmental parameters (intercellular space, intracellular content within the diverse eukaryotic cells).

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Structural Basis for Antibody Recognition of Lipid A

Cited by 11 publications

References 63 publications

Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus mirabilis O3 (S1959) Lipopolysaccharide May React with Collagen Type I

Antibodies Isolated from Rheumatoid Arthritis Patients against Lysine-Containing Proteus mirabilis O3 (S1959) Lipopolysaccharide May React with Collagen Type I

A Germline-Encoded Structural Arginine Trap Underlies the Anti-DNA Reactivity of a Murine V Gene Segment

Yersinia pseudotuberculosis-derived adhesins

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