Death, adaptation and regulation: The three pillars of immune tolerance restrict the risk of autoimmune disease caused by molecular mimicry

Ryan, Kelli R.; Patel, Sarju D.; Stephens, Leigh A.; Anderton, Stephen M.

doi:10.1016/j.jaut.2007.07.014

Cited by 49 publications

(25 citation statements)

References 72 publications

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“…Even though the immune system encounters mimicry very often, it does not always result in autoimmunity (36). Hence, the mechanisms by which the immune system addresses the structural equivalences at the molecular level are of great relevance.…”

Section: Discussionmentioning

confidence: 99%

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Tapryal

Gaur

Kaur

et al. 2013

The Journal of Immunology

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Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature. It also occurs when a flexible paratope accommodates dissimilar Ags by adjusting structural features according to the antigenic epitopes or differential positioning in the Ag combining site. Toward deciphering the structural basis of molecular mimicry, mAb 2D10 was isolated from a maturing immune response elicited against methyl α-d-mannopyranoside and also bound equivalently to a dodecapeptide. The physicochemical evidence of this carbohydrate–peptide mimicry in the case of mAb 2D10 had been established earlier. These studies had strongly suggested direct involvement of a flexible paratope in the observed mimicry. Surprisingly, comparison of the Ag-free structure of single-chain variable fragment 2D10 with those bound to sugar and peptide Ags revealed a conformationally invariant state of the Ab while binding to chemically and structurally disparate Ags. This equivalent binding of the two dissimilar Ags was through mutually independent interactions, demonstrating functional equivalence in the absence of structural correlation. Thus, existence of a multispecific, mature Ab in the secondary immune response was evident, as was the plasticity in the interactions while accommodating topologically diverse Ags. Although our data highlight the structural basis of receptor multispecificity, they also illustrate mechanisms adopted by the immune system to neutralize the escape mutants generated during pathogenic insult.

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Section: Discussionmentioning

confidence: 99%

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Tapryal

Gaur

Kaur

et al. 2013

The Journal of Immunology

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“…Indeed, autoimmunity is prominent in CVID [52,59,60,61] and 23–50% of patients manifest unclassified autoimmune features [28,62]. The mechanisms that lead to loss of tolerance in patients with immune deficiency as well as the same generic issue in autoimmune disease have been recently discussed [62,63,64,65,66,67,68,69,70,71,72]. In patients with X-linked agammaglobulinemia, a non-CVID disorder characterized by an extremely reduced B cell count, the remaining B cells are enriched in autoreactive clones [73].…”

Section: Cvid Clinical Featuresmentioning

confidence: 99%

Common Variable Immunodeficiency: Etiological and Treatment Issues

Deane

Selmi

Naguwa

et al. 2009

Int Arch Allergy Immunol

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One of the great advances in clinical medicine was the recognition of the pleomorphism of the immune response and the multiple afferent and efferent limbs of antigen processing and responsiveness. A significant contribution to this understanding was derived from studies of human immunodeficiency states, including both inherited and acquired syndromes. Amongst these syndromes, one of the most common, and least understood, is common variable immune deficiency (CVID). CVID is a syndrome that leads to a reduction in serum immunoglobulins and complications including recurrent infections. Management includes immunoglobulin replacement therapy; however, patients with CVID are at risk for complications of exogenous immunoglobulin administration as well as CVID-associated diseases such as autoimmune processes and malignancies. To assess the current state of knowledge in the field, we performed a literature review of a total of 753 publications covering the period of 1968 until 2008. From this list, 189 publications were selected for discussion. In this review, we demonstrate that while the molecular basis of CVID in many cases remains incompletely understood, significant strides have been made and it is now clear that there is involvement of several pathways of immune activation, with contributions from both T and B cells. Furthermore, despite the current gaps in our knowledge of the molecular pathogenesis of the syndrome, there have been dramatic advances in management that have led to improved survival and significantly reduced morbidity in affected patients.

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“…We should note that GCA has a strong correlation with polymyalgia rheumatica (PMR), but this will not be discussed within this manuscript. We will also not discuss either the mechanisms of the immune response or related themes in vasculitis, but rather refer the reader to recent literature on not only polymyalgia rheumatica, but also vasculitis and methodologies used to decipher the etiologies of other rheumatic diseases [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The Geo-epidemiology of Temporal (Giant Cell) Arteritis

Lee

Naguwa

Cheema

et al. 2008

Clinic Rev Allerg Immunol

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Giant cell arteritis (GCA) is the most common vasculopathy in patients over the age of 50. The majority of data on the geo-epidemiology of GCA is derived from Scandinavia, although there is very good documentation and epidemiological descriptions from studies throughout Europe and North America. There remains, however, a paucity of data on the incidence and prevalence of GCA in North American minority populations, as well as from Africa or Asia. The data that does exist suggests that the incidence of GCA is lower in Hispanic, Asian, and African American populations. It is interesting to note that as the population throughout the world continues to age, we anticipate an increased prevalence of disease based upon increases in annual incidence and improved survival. Considerable research is still needed to identify genetic, environmental, and gender-specific factors that influence not only the etiology, but also the natural history of disease.

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Death, adaptation and regulation: The three pillars of immune tolerance restrict the risk of autoimmune disease caused by molecular mimicry

Cited by 49 publications

References 72 publications

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Common Variable Immunodeficiency: Etiological and Treatment Issues

The Geo-epidemiology of Temporal (Giant Cell) Arteritis

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