Antibody specificity and promiscuity

2019 ◽  
Vol 476 (3) ◽  
pp. 433-447 ◽  
Author(s):  
Deepti Jain ◽  
Dinakar M. Salunke
Keyword(s):  
Immune System ◽  
Molecular Mimicry ◽  
A Priori ◽  
Rapid Evolution ◽  
Cross Reactivity ◽  
Immune Defense ◽  
Autoimmune Response ◽  
Antigenic Determinants ◽  
Antibody Specificity ◽  
Foreign Antigen

Abstract The immune system is capable of making antibodies against anything that is foreign, yet it does not react against components of self. In that sense, a fundamental requirement of the body's immune defense is specificity. Remarkably, this ability to specifically attack foreign antigens is directed even against antigens that have not been encountered a priori by the immune system. The specificity of an antibody for the foreign antigen evolves through an iterative process of somatic mutations followed by selection. There is, however, accumulating evidence that the antibodies are often functionally promiscuous or multi-specific which can lead to their binding to more than one antigen. An important cause of antibody cross-reactivity is molecular mimicry. Molecular mimicry has been implicated in the generation of autoimmune response. When foreign antigen shares similarity with the component of self, the antibodies generated could result in an autoimmune response. The focus of this review is to capture the contrast between specificity and promiscuity and the structural mechanisms employed by the antibodies to accomplish promiscuity, at the molecular level. The conundrum between the specificity of the immune system for foreign antigens on the one hand and the multi-reactivity of the antibody on the other has been addressed. Antibody specificity in the context of the rapid evolution of the antigenic determinants and molecular mimicry displayed by antigens are also discussed.

Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus

Lupus ◽  
2009 ◽  
Vol 18 (13) ◽  
pp. 1136-1143 ◽  
Author(s):  
M. Blank ◽  
Y. Shoenfeld ◽  
A. Perl
Keyword(s):  
Lupus Erythematosus ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Stress Hormones ◽  
Cross Reactivity ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Autoimmune Response ◽  
Human Endogenous Retroviruses ◽  
Ultraviolet Exposure

Environmental factors are capable of triggering the expression of human endogenous retroviruses and induce an autoimmune response. Infection can promote the expression of human endogenous retroviruses by molecular mimicry or by functional mimicry. There are additional mechanisms which may control the expression of human endogenous retroviruses, such as epigenetic status of the genome (hypomethylation, histone deacetylation). Ultraviolet exposure, chemicals/drugs, injury/stress, hormones, all as a single cause or in a concert, may modulate the involvement of human endogenous retroviruses in pathogenic processes. In the current review we summarize the current knowledge on infections, molecular mimicry, cross-reactivity and epigenetics contribution for trigger human endogenous retroviruses expression and pathogenesis in lupus patients. Lupus (2009) 18, 1136—1143.

scholarly journals GAKG-RGEKG an Epitope That Provokes Immune Cross-Reactivity betweenPrevotellasp. and Human Collagen: Evidence of Molecular Mimicry in Chronic Periodontitis

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Gustavo Alberto Obando-Pereda
Keyword(s):  
Immune System ◽  
Periodontal Disease ◽  
Molecular Mimicry ◽  
Hypothetical Protein ◽  
Cross Reactivity ◽  
World Population ◽  
Human Economy ◽  
Human Proteins ◽  
Human Collagen ◽  
Antigen Presenting

Periodontal disease afflicts 20% of world population. This process usually occurs in the form of being lethargic and chronic, and consequently this disease is known as chronic process. All chronic diseases constantly cause activation of the immune system, and therefore the presentation of microbial peptides which are presented to lymphocytes by professional antigen presenting cells can present microbial peptides very similar to important structures of human economy causing autoimmune diseases, process known as molecular mimicry. Thus, the aim of this study was to verify the presence of molecular mimicry phenomenon between periodontopathogens and human proteins. Blasting microbes of Socransky periodontal complexes against human collagen were performed and then the proteins with similarities were modelled and were screened in the MHI binding virtual methods. The epitopes selected were produced and plasma of chronic periodontal volunteers was obtained and a dot immunobinding assay was performed. Hypothetical protein ofPrevotellasp. and human collagen epitopes with high similarities were positive for dot immunobinding assay. With this result it can be suggested that the mimicry phenomena can occur on periodontal disease.

scholarly journals Sialic Acid-Siglec Axis as Molecular Checkpoints Targeting of Immune System: Smart Players in Pathology and Conventional Therapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4361
Author(s):  
Przemyslaw Wielgat ◽  
Karol Rogowski ◽  
Katarzyna Niemirowicz-Laskowska ◽  
Halina Car
Keyword(s):  
Immune System ◽  
Sialic Acid ◽  
Cancer Therapy ◽  
Conventional Therapy ◽  
Regulatory Mechanism ◽  
Molecular Mimicry ◽  
Cross Reactivity ◽  
Immune Checkpoints ◽  
Molecular Targeting ◽  
Malignant Cells

The sialic acid-based molecular mimicry in pathogens and malignant cells is a regulatory mechanism that leads to cross-reactivity with host antigens resulting in suppression and tolerance in the immune system. The interplay between sialoglycans and immunoregulatory Siglec receptors promotes foreign antigens hiding and immunosurveillance impairment. Therefore, molecular targeting of immune checkpoints, including sialic acid-Siglec axis, is a promising new field of inflammatory disorders and cancer therapy. However, the conventional drugs used in regular management can interfere with glycome machinery and exert a divergent effect on immune controlling systems. Here, we focus on the known effects of standard therapies on the sialoglycan-Siglec checkpoint and their importance in diagnosis, prediction, and clinical outcomes.

scholarly journals The Evolutionary Origin of the Immune System, Neonatal Tolerance, Mhc Restriction

2017 ◽  
Vol 1 (1) ◽  
pp. 01-05
Author(s):  
Sunitha Cherukur ◽  
Garrepally Prasad
Keyword(s):  
Immune System ◽  
Antigen Processing ◽  
Malignant Tumors ◽  
Clonal Selection ◽  
Cross Reactivity ◽  
Evolutionary Origin ◽  
Antigenic Determinants ◽  
Immune Recognition ◽  
Chronic Infections ◽  
Clonal Selection Theory

Immunology has made tremendous progress during more than half century after Burnet's clonal selection theory was published, but there are still more questions than answers. What is the function of the immune system, given that invertebrates have lived without one for millions of years, although they are also susceptible to infections and tumors? On the other hand, the emergence of the immune system in evolution did not deliver higher animals from either infections or cancer. The concept of linked functions is an attempt at answering these and other related questions. The concept assumes that the evolutionary origin of the immune system is related to a primary nonimmune function rather than to self/ nonself recognition. However, the mechanisms used to fulfill this function proved to be a suitable basis for immune recognition, which, according to the concept, occurs at the level of receptor-bearing immune cells rather than receptors themselves. Since cross-reactivity is a common phenomenon, it is assumed that specific combinations of antigenic determinants, rather than determinants per se, serve as recognition criteria, antigen processing and MCH-II restriction being necessary steps of the immune recognition of these combinations. The new views on adaptive immunity suggest new approaches to preventing graft rejection and treating chronic infections and malignant tumors.

scholarly journals S184. IN SILICO PREDICTION OF T-CELL-MEDIATED MOLECULAR MIMICRY IN TOXOPLASMOSIS AND SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S108-S108
Author(s):  
David Thylur ◽  
Adriana Lori ◽  
Dimitri Avramopoulos ◽  
Jennifer Mulle ◽  
Fernando Goes ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
In Silico ◽  
Molecular Mimicry ◽  
Adaptive Immune System ◽  
Autoimmune Response ◽  
Host Proteins ◽  
Adaptive Immune ◽  
Local Sequence

Abstract Background Exposure to Toxoplasma gondii (TOXO) has been consistently associated with the development of schizophrenia, but the neurobiological mechanism through which this occurs is not well elucidated. Emerging data has broadly implicated the adaptive immune system as a possible pathway from TOXO infection to schizophrenia. In order to explore the hypothesis that crossreactive T cells could help mediate this relationship, we built upon the genetic analysis from our psychiatrically-enriched Ashkenazi Jewish cohort using an in silico approach to predict HLA reactivity to TOXO epitopes, with the aim of identifying host proteins that could be susceptible to T-cell-mediated molecular mimicry. Methods We used netMHCpan v4.0 to generate a library of 2182 oligopeptides from the TOXO proteome that were predicted to be strongly antigenic for individuals with HLA-C*04:01, an allele of interest since our analysis indicated that the odds ratio for TOXO infection were in the opposite direction for those with schizophrenia compared to controls. A predicted binding affinity less than 500 nM was used to identify epitopes that were likely to be biologically relevant. Epitopes identified by this approach were compared with human peptides for local sequence similarity using BLAST optimized for short peptide sequences in order to identify host proteins that could mimic TOXO antigens. Ingenuity Pathway Analysis was then used to interpret and synthesize possible biological relationships between predicted autoantigens and schizophrenia. Results Our pipeline identified 38 candidate proteins for molecular mimicry at a threshold of P<.05 after correcting for multiple testing. A number of these genes have been strongly linked to schizophrenia through genetic studies, including HSPA9, PSMA4, and ZDHHC5. Pathway and gene ontology analysis revealed that these genes were involved in networks of regulation of gene expression as well as ubiquitination, which participates in antigen presentation. Discussion Using an in silico approach, we identified 38 human proteins that could be targeted by a crossreactive T cell autoimmune response after exposure to TOXO. Several of these candidate proteins are highly relevant for genetic risk of schizophrenia and participate in molecular pathways that mediate antigen processing. CD8+ T cells contribute to autoimmunity through cytokine release and have been implicated in the relationship between TOXO exposure and schizophrenia. Though these results will need experimental confirmation, we hope that they will spur further research on the role of the adaptive immune system in toxoplasmosis and schizophrenia.

scholarly journals Synthetic mycobacterial diacyl trehaloses reveal differential recognition by human T cell receptors and the C-type lectin Mincle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Josephine F. Reijneveld ◽  
Mira Holzheimer ◽  
David C. Young ◽  
Kattya Lopez ◽  
Sara Suliman ◽  
...  
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Immune System ◽  
T Cell ◽  
Cross Reactivity ◽  
Lipid Binding ◽  
Human Immune System ◽  
Human T Cell ◽  
Human T Cells ◽  
Pure Compounds

AbstractThe cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system.

scholarly journals Thromboses and Hemostasis Disorders Associated with Coronavirus Disease 2019: The Possible Causal Role of Cross-Reactivity and Immunological Imprinting

2021 ◽  
Author(s):  
Darja Kanduc
Keyword(s):  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Natural Infection ◽  
Vascular Diseases ◽  
Cross Reactivity ◽  
Active Immunization ◽  
Thromboembolic Complications ◽  
Human Proteins ◽  
Almost All

AbstractBy examining the issue of the thromboses and hemostasis disorders associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) through the lens of cross-reactivity, it was found that 60 pentapeptides are shared by SARS-CoV-2 spike glycoprotein (gp) and human proteins that— when altered, mutated, deficient or, however, improperly functioning— cause vascular diseases, thromboembolic complications, venous thrombosis, thrombocytopenia, coagulopathies, and bleeding, inter alia. The peptide commonality has a relevant immunological potential as almost all of the shared sequences are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes, thus supporting the possibility of cross-reactions between the viral gp and the thromboses-related human proteins. Moreover, many of the shared peptide sequences are also present in pathogens to which individuals have previously been exposed following natural infection or vaccinal routes, and of which the immune system has stored imprint. Such an immunological memory might rapidly trigger anamnestic secondary cross-reactive responses of extreme affinity and avidity, in this way explaining the thromboembolic adverse events that can associate with SARS-CoV-2 infection or active immunization.

scholarly journals The Emerging Role of Macrophages in Immune System Dysfunction under Real and Simulated Microgravity Conditions

2021 ◽  
Vol 22 (5) ◽  
pp. 2333
Author(s):  
Yulong Sun ◽  
Yuanyuan Kuang ◽  
Zhuo Zuo
Keyword(s):  
Immune System ◽  
Mapk Signaling ◽  
Immune Defense ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Drugs ◽  
Physiological Processes ◽  
Immune System Dysfunction ◽  
Cell Immunity ◽  
Mitogen Activated Protein ◽  
Microgravity Conditions

In the process of exploring space, the astronaut’s body undergoes a series of physiological changes. At the level of cellular behavior, microgravity causes significant alterations, including bone loss, muscle atrophy, and cardiovascular deconditioning. At the level of gene expression, microgravity changes the expression of cytokines in many physiological processes, such as cell immunity, proliferation, and differentiation. At the level of signaling pathways, the mitogen-activated protein kinase (MAPK) signaling pathway participates in microgravity-induced immune malfunction. However, the mechanisms of these changes have not been fully elucidated. Recent studies suggest that the malfunction of macrophages is an important breakthrough for immune disorders in microgravity. As the first line of immune defense, macrophages play an essential role in maintaining homeostasis. They activate specific immune responses and participate in large numbers of physiological activities by presenting antigen and secreting cytokines. The purpose of this review is to summarize recent advances on the dysfunction of macrophages arisen from microgravity and to discuss the mechanisms of these abnormal responses. Hopefully, our work will contribute not only to the future exploration on the immune system in space, but also to the development of preventive and therapeutic drugs against the physiological consequences of spaceflight.

scholarly journals Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 885
Author(s):  
Georgia Fousteri ◽  
Amy Dave Jhatakia
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Viral Infections ◽  
Molecular Mimicry ◽  
Short Review ◽  
Organ Damage ◽  
Lymphocytic Choriomeningitis ◽  
Immune Deviation ◽  
Viral Pathogen ◽  
Lcmv Infection

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

scholarly journals Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

1995 ◽  
Vol 182 (1) ◽  
pp. 59-65 ◽  
Author(s):  
I Ferrari ◽  
M J Levin ◽  
G Wallukat ◽  
R Elies ◽  
D Lebesgue ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Adrenergic Receptor ◽  
Molecular Mimicry ◽  
Autoimmune Response ◽  
Extracellular Loop ◽  
Western Blots ◽  
Carboxy Terminal ◽  
Ribosomal Protein P0 ◽  
Positive Chronotropic Effect

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

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