Proliferative responses to selected peptides of IA-2 in identical twins discordant for Type 1 diabetes

Schulz, Renate; Hawa, M.; Leslie, R. D. G.; Sinigaglia, Francesco; Passini, Nadia; Rogge, Lars; Picard, J; Londei, Marco

doi:10.1002/1520-7560(0000)9999:9999<::aid-dmrr101>3.0.co;2-2

Cited by 8 publications

(3 citation statements)

References 34 publications

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“…[99][100]. While a number of epitopes from the three main autoantigens have been identified, specific for CD4 + cells from peripheral blood of newly-diagnosed patients, it has not been possible to establish their relative importance in pathogenesis [71][72][73][74][75][101][102][103][104][105]; it is still unresolved, for example, if disease pathogenesis commences with responsiveness to a few primary epitopes, with consequential and orderly epitope spreading, or whether there is a "random hit" mechanism at first, and a generalized breakdown of tolerance to autoantigen epitopes thereafter. This is particularly so for the CD4 epitopes, as they reflect restriction to the HLA-DQ alleles conferring susceptibility to the disease.…”

Section: Type 1 Diabetes Mellitusmentioning

confidence: 83%

“…Yet, there have been several counter-examples to this, rendering the generalization a poor one [42,43,70]. Likewise, there have been cases where residues p-1, p-2, even p-4, and p10 appeared significant for T cell recognition [71][72][73][74][75]. As such residues are clearly outside the canonical footprint of the TCR, hence not in contact with it, such effects can have two possible explanations: a. that the presence of these substitutions causes subtle changes in their proximal MHC II and peptide residues that are part of the TCR footprint, affecting thus indirectly such an interaction.…”

Section: The Mhc Ii-peptide-tcr Complexmentioning

confidence: 99%

“…The particular gluten epitopes are quite different from the HLADQ2cis and -DQ8cis epitopes to which pathogenic CD4 + T cells isolated from small intestinal biopsies of CD patients are sensitized [134][135][136][137][138]. This is perhaps an indication that fulminant autoimmune disease will lead to a more generalized breakdown of tolerance to the specific autoantigen(s), not restricted to the MHC II-disease related allele(s); such T cell clones will be evident in the peripheral blood, and have already been detected in patients with type 1 diabetes [71][72][73][74][75].…”

Section: Celiac Diseasementioning

confidence: 99%

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Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases

Moustakas

Papadopoulos²

2009

CPD

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The Major Histocompatibility Complex Class II locus is the primary genetic linkage to autoimmune diseases. Susceptibility to each such disease is linked to different alleles, with a few alleles showing also dominant protection. The design of vaccines for autoimmune diseases is a long sought-after goal. As knowledge about the pathogenesis of these diseases has increased, the tools for such an approach have of necessity been refined. We review below the structural essence of MHC II-linked autoimmune diseases which centers on the binding of antigenic peptides to the disease-linked MHC II proteins, and the consequent activation of cognate TCRs from pathogenic CD4+ T cells. The state of affairs in two organ-specific autoimmune diseases, type 1 diabetes, celiac disease are covered, including attempts to treat these via antigen-specific MHC II-guided measures. We offer a couple of testable suggestions as to how this approach could be improved.

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Section: Type 1 Diabetes Mellitusmentioning

confidence: 83%

Section: The Mhc Ii-peptide-tcr Complexmentioning

confidence: 99%

Section: Celiac Diseasementioning

confidence: 99%

See 1 more Smart Citation

Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases

Moustakas

Papadopoulos²

2009

CPD

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Current Awareness

2000

Diabetes Metab. Res. Rev.

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books, Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Prediction; 7 Prevention; 8 Intervention: a) General; b) Pharmacology; 9 Pathology: a) General; b) Cardiovascular; c) Neurological; d) Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13 Techniques. Within each section, articles are listed in alphabetical order with respect to author (11 Weeks journals ‐ Search completed at 6th Sept. 2000)

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Molecular properties of HLA‐DQ alleles conferring susceptibility to or protection from insulin‐dependent diabetes mellitus: Keys to the fate of islet β‐cells

Moustakas

Papadopoulos

2002

Am. J. Med. Genet.

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The major histocompatibility complex Class II alleles, HLA-DQ, and the related HLA-DR, are the chief genetic elements of human type 1 diabetes. These genes code for polymorphic heterodimeric proteins, whose chief function is to trap peptide antigens in the endosome and present them on the surface of antigen-presenting cells (dendritic cells, B lymphocytes, monocytes/macrophages) to CD4(+) T helper cells. A systematic investigation of the molecular properties of HLA-DQ alleles linked to susceptibility or resistance to type 1 diabetes has shown that these properties segregate along lines of susceptibility or resistance. A correlation of these features with the function of each particular segment of the HLA-DQ molecule yields interesting insights into the possible pathways leading to type 1 diabetes. There remain, however, areas to be clarified, including mechanisms by which dominant protection is conferred by certain alleles, the interplay between HLA-DQ and the related locus HLA-DR, that also shows autoantigen-specific reactivity, and the cross-Class help delivered to CD8(+) T cells, the final effectors in pancreatic beta-cell destruction. Clarification of these issues may lead to ways to prevent diabetes in predisposed individuals already exhibiting the genetic and immunological characteristics, and perhaps a cure in those with the disease, by means of transplantation, and measures for prevention of disease recurrence.

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Proliferative responses to selected peptides of IA-2 in identical twins discordant for Type 1 diabetes

Cited by 8 publications

References 34 publications

Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases

Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases

Current Awareness

Molecular properties of HLA‐DQ alleles conferring susceptibility to or protection from insulin‐dependent diabetes mellitus: Keys to the fate of islet β‐cells

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