Identification of mimicry peptides based on sequential motifs of epitopes derived from 65-kDa glutamic acid decarboxylase

Bach, Jean-Marie; Otto, H; Jung, Günther; Cohen, H.; Boîtard, Christian; Bach, Jean‐François; Endert, Peter M. van

doi:10.1002/(sici)1521-4141(199806)28:06<1902::aid-immu1902>3.0.co;2-j

Cited by 21 publications

(5 citation statements)

References 30 publications

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“…8 Strong stimulation of GAD65-specific T-cell lines by HHV-6 U2 antigen due to molecular mimicry has been previously shown. 15 Also, release of intracellular GAD or other potential antigens from virus-infected parenchymal cells could contribute to autoimmunity in a susceptible host. The case of this patient may constitute an intriguing pathogenic concept.…”

Section: Discussionmentioning

confidence: 99%

Non‐paraneoplastic limbic encephalitis and central nervous HHV‐6B reactivation: Causality or coincidence?

et al. 2016

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Autoantibody-related encephalopathies represent an important differential diagnosis in adult onset epilepsy. Here, we report the case of a 25-year-old patient with new-onset epilepsy and psychotic syndrome, who underwent biopsy resection for etiological classification. MRI analysis and neuropathological examination showed a T-lymphocytic dominated encephalitis with involvement of the limbic system. An indirect immunohistochemistry approach identified autoantibodies against glutamic acid decarboxylase (GAD) in cerebral spinal fluid and serum, which were confirmed by affinity purification / mass spectrometry analysis. Further examinations revealed evidence of chromosomally integrated human herpes virus type 6B (HHV-6B). However, astrocytic expression of HHV-6 lytic protein was detected by double immunofluorescence analysis. The cerebral expression of HHV-6 antigen, a clinical improvement under antiviral therapy as well as an initial finding of HHV-6 IgM antibodies strongly argue for an additional active HHV-6B infection. Review of the literature reveals singular reports of patients with GAD antibody-positive limbic encephalitis and central nervous system infections with HHV-6B. Since herpes simplex virus encephalitis has been recently reported as a trigger of N-methyl-D-aspartate receptor antibody encephalitis, it is tempting to speculate that HHV-6B infections may trigger a non-paraneoplastic form of limbic encephalitis in a parallel cascade.

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Section: Discussionmentioning

confidence: 99%

Non‐paraneoplastic limbic encephalitis and central nervous HHV‐6B reactivation: Causality or coincidence?

et al. 2016

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“…Bacterial peptides homologous to PDC-E2 159-167, identified by BLAST search, were also synthesized ( Table 2). A previously defined HLA-A*0201-restricted CTL epitope, amino acids 18-27 of the hepatitis B virus core protein (HBc [18][19][20][21][22][23][24][25][26][27] ), 28 and amino acids 57-66 of the influenza matrix protein (FluMP 57-66 ) 29 were used as antigen-specific negative controls. All peptides were synthesized with a free NH2 and a free COOH terminus, and their purity was confirmed by HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…[10][11][12]16,17 Thus, the determination of class I-restricted immunodominant epitopes of self antigens coupled by an understanding of the structural basis of T-cell recognition of autoantigens, such as TCR contact and MHC-binding residues, are of potential importance in providing a means of manipulating the immune response to self antigens. [18][19][20][21][22][23][24][25][26][27] These thoughts prompted us to study the potential antigenicity of the analogue peptides derived from amino acids 159-167 of PDC-E2, which is an HLA-A*0201-restriced CTL epitope, in PBC patients. HLA-A*0201 binding of these peptides and CTL recognition of these same peptides in the context of HLA-A*0201 were analyzed to define the peptide exhibiting antagonistic effect on the CTLs.…”

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confidence: 99%

Analysis of TCR antagonism and molecular mimicry of an HLA-A*0201-restricted CTL epitope in primary biliary cirrhosis

Kita

Matsumura

et al. 2002

Hepatology

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Although the etiology and mechanism of primary biliary cirrhosis (PBC) is unknown, growing evidence suggests a major role for T cells. We have recently identified the first CD8 T-cell epitope, amino acid 159-167 of the E2 component of pyruvate dehydrogenase complexes (PDC-E2). To seek for analogue peptide-antagonizing effector function of CTLs specific for this autoantigen, we examined the effector functions of the PDC-E2-specific CTLs against alanine substituted peptides. Furthermore, because molecular mimicry has been postulated as a possible cause of initiating PBC, we carried out studies aimed at identifying naturally occurring peptides for the 159-167 peptide of PDC-E2 that may serve as agonists. An alanine substitution at position 5 of this epitope significantly reduced peptide-specific effector functions of CTLs. Moreover, this analogue peptide inhibited effector functions of the CTLs to the prototype peptide, including cytotoxicity and IFN-␥ production. We also identified a peptide derived from Pseudomonas aeruginosa, which showed a higher binding affinity to the HLA-A*0201 than the prototype peptide. This homologous peptide was recognized by CTLs specific for the prototype epitope on PDC-E2. In conclusion, a modification of the immunodominant autoepitope can be utilized to manipulate the CD8 T-cell responses against the autoantigen PDC-E2. Our finding also supports the thesis that molecular mimicry may be implicated in the initiation of the autoreactive CD8 T-cell responses and has implications for the use of such peptides for immunotherapy. (HEPATOLOGY 2002;36:918-926.)

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“…Influenza and SARS contain many examples of amino acid sequences with homology to these probable ACTH key residues (see Table 2). Ex- actly matching 3 of 6 key residues represents likely antigenic homology, considering that exact matches of only 1 or 2 key residues has been shown to induce significant T cell activation by molecular mimics in other viral agents [4][5][6][7][8].…”

Section: Influenza Hemagglutininmentioning

confidence: 99%

Molecular mimicry of ACTH in SARS – implications for corticosteroid treatment and prophylaxis

Wheatland¹

2004

Medical Hypotheses

116

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For a virus to survive and replicate in an organism, it must employ strategies to evade and misdirect the host's immune response. There is compelling evidence that the primary immunoevasive strategy utilized by the SARS virus, like influenza, is to inhibit its host's corticosteroid stress response. This is accomplished by viral expression of amino acid sequences that are molecular mimics of the host's adrenocorticotropin hormone (ACTH). When the host produces antibodies against these viral antigens, the antibodies also bind to the host's own ACTH, which limits the host's stress response by interfering with ACTH's ability to stimulate the secretion of corticosteroids. This inadequate corticosteroid response provokes symptoms as a result of a relative adrenocortical insufficiency. Treatment with corticosteroids can relieve the patient's symptoms of adrenocortical insufficiency and give them the corticosteroid levels needed to fight their infection. Similarly, by taking moderate daily doses of corticosteroids as a prophylactic, it may be possible to avoid clinical infection with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started, SARS's ability to evade its host's immune system while its viral load is low will be significantly impaired. In this article, amino acid sequences from the SARS and influenza viruses representing likely homology to human ACTH are identified. Evidence demonstrating that ACTH autoantibodies are produced during influenza infection is also presented. Early treatment with corticosteroids should lower the dose necessary to counteract SARS's ACTH autoantibody mechanism. If corticosteroid treatment is delayed until inflammatory cytokine levels are causing serious injury, only high doses of corticosteroids are likely to be effective.

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Identification of mimicry peptides based on sequential motifs of epitopes derived from 65-kDa glutamic acid decarboxylase

Cited by 21 publications

References 30 publications

Non‐paraneoplastic limbic encephalitis and central nervous HHV‐6B reactivation: Causality or coincidence?

Non‐paraneoplastic limbic encephalitis and central nervous HHV‐6B reactivation: Causality or coincidence?

Analysis of TCR antagonism and molecular mimicry of an HLA-A*0201-restricted CTL epitope in primary biliary cirrhosis

Molecular mimicry of ACTH in SARS – implications for corticosteroid treatment and prophylaxis

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