Recognition of Physiological Receptors by Anti-Idiotypic Antibodies: Molecular Mimicry of the Ligand or Cross-Reactivity?

1985 ◽  
pp. 91-110 ◽  
Author(s):  
A. D. Strosberg ◽  
J. G. Guillet ◽  
S. Chamat ◽  
J. Hoebeke
Keyword(s):  
Molecular Mimicry ◽  
Cross Reactivity

scholarly journals Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Monica Goldberg-Murow ◽  
Carlos Cedillo-Peláez ◽  
Luz Elena Concha-del-Río ◽  
Rashel Cheja-Kalb ◽  
María José Salgar-Henao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mimicry ◽  
Clinical Manifestations ◽  
Protective Role ◽  
Cross Reactivity ◽  
Ocular Toxoplasmosis ◽  
Cerebral Toxoplasmosis ◽  
Blood Retinal Barrier ◽  
The Central Nervous System

Toxoplasma gondii infection can trigger autoreactivity by different mechanisms. In the case of ocular toxoplasmosis, disruption of the blood-retinal barrier may cause exposure of confined retinal antigens such as recoverin. Besides, cross-reactivity can be induced by molecular mimicry of parasite antigens like HSP70, which shares 76% identity with the human ortholog. Autoreactivity can be a determining factor of clinical manifestations in the eye and in the central nervous system. We performed a prospective observational study to determine the presence of autoantibodies against recoverin and HSP70 by indirect ELISA in the serum of 65 patients with ocular, neuro-ophthalmic and congenital cerebral toxoplasmosis. We found systemic autoantibodies against recoverin and HSP70 in 33.8% and 15.6% of individuals, respectively. The presence of autoantibodies in cases of OT may be related to the severity of clinical manifestations, while in cases with CNS involvement they may have a protective role. Unexpectedly, anti-recoverin antibodies were found in patients with cerebral involvement, without ocular toxoplasmosis; therefore, we analyzed and proved cross-reactivity between recoverin and a brain antigen, hippocalcin, so the immunological phenomenon occurring in one immune-privileged organ (e.g. the central nervous system) could affect the environment of another (egg. the eye).

scholarly journals Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization

2012 ◽  
Vol 130 (1) ◽  
pp. 248-256.e9 ◽  
Author(s):  
Helton C. Santiago ◽  
Elyse LeeVan ◽  
Sasisekhar Bennuru ◽  
Flavia Ribeiro-Gomes ◽  
Ellen Mueller ◽  
...  
Keyword(s):  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Glutathione S Transferases

scholarly journals Antibodies from a Patient with Type 1 Diabetes and Celiac Disease Bind to Macrophages that Express the Scavenger Receptor CD163

2011 ◽  
Vol 25 (6) ◽  
pp. 327-329 ◽  
Author(s):  
Brigitte Sonier ◽  
Alexander Strom ◽  
Gen-Sheng Wang ◽  
Christopher Patrick ◽  
Jennifer A Crookshank ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Molecular Mimicry ◽  
Scavenger Receptor ◽  
Cross Reactivity ◽  
Rat Jejunum ◽  
The Novel ◽  
Blood Monocytes ◽  
Specific Subset

Antibodies against the wheat storage globulin Glo-3A from a patient with both type 1 diabetes (T1D) and celiac disease were enriched to identify potential molecular mimicry between wheat antigens and T1D target tissues. Recombinant Glo-3A was used to enrich anti-Glo-3A immunoglobulin G antibodies from plasma by batch affinity chromatography. Rat jejunum and pancreas, as well as human duodenum and monocytes were probed, and binding was evaluated by immunohistochemistry and confocal microscopy. Glo-3A-enriched antibodies bound to a specific subset of cells in the lamina propria of rat jejunum that co-localized mostly with a marker of resident, alternatively activated CD163-positive (CD163+) macrophages. Blood monocytes and macrophage-like cells in human duodenum were also labelled with the enriched antibodies. Blocking studies revealed that binding to CD163+macrophages was not due to cross-reactivity with anti-Glo-3A antibodies, but rather to non-Glo-3A antibodies co-purified during antibody enrichment. The novel finding of putative autoantibodies against tolerogenic intestinal CD163+macrophages suggests that regulatory macrophages were targeted in this patient with celiac disease and T1D.

scholarly journals Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 162-169 ◽  
Author(s):  
A Bettaieb ◽  
P Fromont ◽  
F Louache ◽  
E Oksenhendler ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Platelet Glycoprotein ◽  
Conformational Structure ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus ◽  
Hiv Antibodies ◽  
Membrane Antigens ◽  
Immunodeficiency Syndrome

We previously reported the presence in platelet eluates of autoantibodies directed against epitopes of the platelet glycoprotein (GP)IIb/IIIa complex in acquired immunodeficiency syndrome (AIDS)-free human immunodeficiency virus (HIV)-infected patients with immunologic thrombocytopenic purpura (ITP). We investigated whether HIV antibodies recognized platelet membrane antigens to determine whether the virus might be directly or indirectly responsible for the thrombocytopenia in this context. Direct eluates of platelets from 25 patients with HIV- related ITP contained IgG reacting with HIV-GP160/120 and also, in 45% of patients, detectable antiplatelet antibodies, immunochemically characterized as anti-GPIIb and/or anti-GPIIIa in 5 patients. Furthermore, serum HIV-GP160/120 antibodies could be absorbed on and eluted from platelets from normal non-HIV-infected healthy blood donors (indirect eluates). In contrast, GP160/120 antibodies present in the serum of nonthrombocytopenic HIV-infected patients were not absorbable on normal platelets in most patients, suggesting a pathogenic role in HIV-related ITP. We performed detailed studies of a patient with the highest titer of both HIV-GP160/120 and GPIIb/IIIa antibodies in direct and indirect platelet eluates. No antibody binding to GPIIb/IIIa- deficient Glanzmann thrombasthenic platelets was detected. Furthermore, binding/elution experiments conducted with insoluble recombinant GP160 (expressed in baculovirus) and purified platelet GPIIb/IIIa demonstrated that the patient's IgG bound specifically, through the F(ab')2 portion, to a common epitope of HIV-GP160/120 and platelet GPIIb/IIIa. This common epitope was present on a recombinant GP160 expressed in baculovirus but absent from another recombinant GP160 expressed in vaccinia virus, suggesting that the cross-reactivity is dependent on the glycosylation or conformational structure of the GP. We conclude that molecular mimicry between HIV-GP160/120 and platelet GPIIb/IIIa may explain at least some cases of ITP in AIDS-free HIV- infected patients.

scholarly journals Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Aristo Vojdani ◽  
Elroy Vojdani ◽  
Datis Kharrazian
Keyword(s):  
Monoclonal Antibodies ◽  
Autoimmune Diseases ◽  
Human Tissue ◽  
Molecular Mimicry ◽  
Disease Process ◽  
Cross Reactivity ◽  
Immune Reactivity ◽  
Human Tissues ◽  
Human Monoclonal Antibodies ◽  
Tissue Antigens

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.

scholarly journals Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach

2020 ◽  
Author(s):  
Hyunsu An ◽  
Jihwan Park
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Web Application ◽  
Molecular Mimicry ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Cross Reactivity ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Human Proteins

ABSTRACTCurrently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.

scholarly journals Cross-Reactivity between the Rheumatoid Arthritis-Associated Motif EQKRAA and Structurally Related Sequences Found inProteus mirabilis

1999 ◽  
Vol 67 (6) ◽  
pp. 2769-2775 ◽  
Author(s):  
Harmale Tiwana ◽  
Clyde Wilson ◽  
Alison Alvarez ◽  
Ramadan Abuknesha ◽  
Sukhvinder Bansal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Collagen Type ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Mouse Fibroblast ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Negative Bacterium ◽  
Underlying Mechanisms ◽  
Similar Peptide

ABSTRACT Cross-reactivity or molecular mimicry may be one of the underlying mechanisms involved in the etiopathogenesis of rheumatoid arthritis (RA). Antiserum against the RA susceptibility sequence EQKRAA was shown to bind to a similar peptide ESRRAL present in the hemolysin of the gram-negative bacterium Proteus mirabilis, and an anti-ESRRAL serum reacted with EQKRAA. There was no reactivity with either anti-EQKRAA or anti-ESRRAL to a peptide containing the EDERAA sequence which is present in HLA-DRB1∗0402, an allele not associated with RA. Furthermore, the EQKRAA and ESRRAL antisera bound to a mouse fibroblast transfectant cell line (Dap.3) expressing HLA-DRB1∗0401 but not to DRB1∗0402. However, peptide sequences structurally related to the RA susceptibility motif LEIEKDFTTYGEE (P. mirabilisurease), VEIRAEGNRFTY (collagen type II) and DELSPETSPYVKE (collagen type XI) did not bind significantly to cell lines expressing HLA-DRB1∗0401 or HLA-DRB1∗0402 compared to the control peptide YASGASGASGAS. It is suggested here that molecular mimicry between HLA alleles associated with RA and P. mirabilis may be relevant in the etiopathogenesis of the disease.

scholarly journals From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity

2021 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Tumor Suppressor ◽  
Severe Acute Respiratory Syndrome ◽  
Molecular Mimicry ◽  
Human Tumor ◽  
Cross Reactivity ◽  
Tumor Suppressor Proteins ◽  
Associated Proteins ◽  
Immune Response To Cancer ◽  
High Level ◽  
Risk Of Cancer

Abstract Background and Objectives Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins. Materials and Methods Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases. Results An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena. Conclusion This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic.

scholarly journals Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 162-169 ◽  
Author(s):  
A Bettaieb ◽  
P Fromont ◽  
F Louache ◽  
E Oksenhendler ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Platelet Glycoprotein ◽  
Conformational Structure ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus ◽  
Hiv Antibodies ◽  
Membrane Antigens ◽  
Immunodeficiency Syndrome

Abstract We previously reported the presence in platelet eluates of autoantibodies directed against epitopes of the platelet glycoprotein (GP)IIb/IIIa complex in acquired immunodeficiency syndrome (AIDS)-free human immunodeficiency virus (HIV)-infected patients with immunologic thrombocytopenic purpura (ITP). We investigated whether HIV antibodies recognized platelet membrane antigens to determine whether the virus might be directly or indirectly responsible for the thrombocytopenia in this context. Direct eluates of platelets from 25 patients with HIV- related ITP contained IgG reacting with HIV-GP160/120 and also, in 45% of patients, detectable antiplatelet antibodies, immunochemically characterized as anti-GPIIb and/or anti-GPIIIa in 5 patients. Furthermore, serum HIV-GP160/120 antibodies could be absorbed on and eluted from platelets from normal non-HIV-infected healthy blood donors (indirect eluates). In contrast, GP160/120 antibodies present in the serum of nonthrombocytopenic HIV-infected patients were not absorbable on normal platelets in most patients, suggesting a pathogenic role in HIV-related ITP. We performed detailed studies of a patient with the highest titer of both HIV-GP160/120 and GPIIb/IIIa antibodies in direct and indirect platelet eluates. No antibody binding to GPIIb/IIIa- deficient Glanzmann thrombasthenic platelets was detected. Furthermore, binding/elution experiments conducted with insoluble recombinant GP160 (expressed in baculovirus) and purified platelet GPIIb/IIIa demonstrated that the patient's IgG bound specifically, through the F(ab')2 portion, to a common epitope of HIV-GP160/120 and platelet GPIIb/IIIa. This common epitope was present on a recombinant GP160 expressed in baculovirus but absent from another recombinant GP160 expressed in vaccinia virus, suggesting that the cross-reactivity is dependent on the glycosylation or conformational structure of the GP. We conclude that molecular mimicry between HIV-GP160/120 and platelet GPIIb/IIIa may explain at least some cases of ITP in AIDS-free HIV- infected patients.

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