A5050991912- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Diabetes Management and Research
- Immunotherapy and Immune Responses
- Celiac Disease Research and Management
- Diabetes Treatment and Management
- Systemic Lupus Erythematosus Research
- Galectins and Cancer Biology
- vaccines and immunoinformatics approaches
- Edible Oils Quality and Analysis
- Viral Infections and Immunology Research
- Rheumatoid Arthritis Research and Therapies
- Botanical Research and Applications
- Helicobacter pylori-related gastroenterology studies
- Genetic Associations and Epidemiology
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Proteins in Food Systems
- Immunodeficiency and Autoimmune Disorders
- Amino Acid Enzymes and Metabolism
- Antifungal resistance and susceptibility
- Transgenic Plants and Applications
Ionian University
2019-2025
Technological Educational Institute of the Ionian Islands
2009-2019
Touro College
2018
Technological Educational Institute of Epirus
2000-2005
University of Ioannina
2002
Howard Hughes Medical Institute
2002
Yale University
2002
University of Bristol
2002
Abstract Objective HLA–DRB1*1001 (DR1001) is a shared epitope allele associated with rheumatoid arthritis (RA). The present study was undertaken to assess the capacity of DR1001 accommodate citrulline in its binding pockets and identify citrullinated T cell epitopes derived from joint‐associated proteins. Methods peptide derivatives containing citrulline, arginine, other amino acid substitutions measured. A prediction algorithm developed arginine‐containing sequences proteins that...
The HLA locus is the strongest risk factor for anti-citrullinated protein antibody (ACPA)+ rheumatoid arthritis (RA). Despite considerable efforts in last 35 years, this association poorly understood. Here we identify (citrullinated) vinculin, present joints of ACPA+ RA patients, as an autoantigen targeted by ACPA and CD4+ T cells. These cells recognize epitope with core sequence DERAA, which also found many microbes protective HLA-DRB1*13 molecules, presented predisposing HLA-DQ molecules....
Insulin is a major target of the autoimmune response associated with destruction pancreatic β cells in type 1 diabetes. A peptide that spans junction insulin B chain and connecting (C) proinsulin has been reported to stimulate T from humans at risk for diabetes diabetes–prone NOD mice. Here we show B24–C36 binds I-Ag7, MHC class II molecule mouse, and, after intranasal administration, induces regulatory CD4+ that, absence CD8+ cells, block adoptive transfer Curiously, however, did not...
Abstract Celiac disease is an enteropathy caused by intolerance to dietary gluten. The disorder strongly associated with DQA1*0501/DQB1*0201 (HLA-DQ2) as ∼95% of celiac patients express this molecule. HLA-DQ2 has unique Ag-binding properties that allow it present a diverse set gluten peptides gluten-reactive CD4+ T cells so instigating inflammatory reaction. Previous work indicated the presence negatively charged amino acids within required for specific binding. This, however, only partly...
HLA-DQ2 and HLA-DQ8 are strongly predisposing haplotypes for type 1 diabetes (T1D). Yet HLA-DQ2/8 heterozygous individuals have a synergistically increased risk compared with or homozygote subjects that may result from the presence of transdimer formed between α-chain (DQA1*05:01) β-chain (DQB1*03:02). We generated cells exclusively expressing this (HLA-DQ8trans), characterized its peptide binding repertoire, defined unique transdimer-specific motif was found to be distinct those HLA-DQ8....
Abstract Because susceptibility to celiac disease is associated strongly with HLA-DQ2 (DQA1*05/DQB1*02) and weakly HLA-DQ8 (DQA1*03/DQB1*03), a subset of patients carries both HLA-DQ8. As result, these may express two types mixed HLA-DQ2/8 transdimers (encoded by DQA1*05/DQB1*03 DQA1*03/DQB1*02) in addition Using T cells from patient expressing HLA-DQ8trans DQA*0501/DQB*0302), but neither nor HLA-DQ8, we demonstrate that this transdimer expressed on the cell surface can present multiple...
Objective The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) incompletely understood. RA high-risk known to share a common motif, the ‘shared susceptibility epitope (SE)’. Here, electropositive P4 pocket of accommodates self-peptide residues containing citrulline but not arginine. His/Phe13β stratifies ACPA-positive RA, while His13βSer polymorphisms stratify ACPA-negative and protection....
HLA-DR genes are associated with the progression from stage 1 and 2 to onset of 3 type diabetes (T1D), after accounting HLA-DQ which they in high linkage-disequilibrium. Based on an integrated cohort participants two completed clinical trials, this investigation finds that sharing a haplotype DRB1*03:01 (DR3) allele, DRB3*01:01:02 *02:02:01 have respectively negative positive associations progression. Further, we uncovered residues (β11, β26, participating pockets 6 4, respectively) DRB3...
The recognition of MHC–peptide complexes by T cells is governed structural considerations that are determined the sequences individual components and their interaction with each other. We have studied function a highly diabetogenic CD8 cell clone specific for insulin B15-23:H-2K d . then related this to modeled structures. native peptide binds poorly H-2K , because small glycine residue at position p9 incapable productive interactions hydrophobic residues pocket F. In addition, electrostatic...
HLA-DQA1*0102-DQB1*0602 is associated with protection against type 1 diabetes (T1D). A similar allele, HLA-DQA1*0102-DQB1*0604, contributes to T1D susceptibility in certain populations but differs only at seven amino acids from HLA-DQA1*0102-DQB1*0602. Five of these polymorphisms are found within the peptide-binding groove, suggesting that differences peptide binding contribute mechanism their association T1D. In this study, we determine motif for HLA-DQA1*0102-DQB1*0604 allelic protein...
OBJECTIVE To explore associations of HLA class II genes (HLAII) with the progression islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Next-generation targeted sequencing was used genotype eight HLAII (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants Diabetes Prevention Trial-1 and Randomized Trial Oral Insulin sponsored by TrialNet. By linkage disequilibrium, DQA1 DQB1 are haplotyped form DQ haplotypes; DP DR...
OBJECTIVE To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with 1/2 who carry HLA DR4-DQ8 and/or have elevated levels IA-2 autoantibodies (IA-2As). RESEARCH AND METHODS Next-generation targeted sequencing technology was used to genotype eight class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants the TrialNet preventative trial (TN07). Baseline against (IAA), GAD65 (GADA), IA-2A were determined prior treatment...
The association of celiac disease (CD) with HLA-DQ2 and HLA-DQ8 is indicative preferential mucosal T cell recognition gluten fragments bound to either DQ allele. We have recently identified two gluten-derived, HLA-DQ8-restricted stimulatory peptides, one each from gliadin glutenin, recognized by specific clones derived the small intestine CD patients. now performed molecular modeling examined fine specificity these peptides in complex HLA-DQ8. There only binding register for both glutamine...
Presentation of citrullinated neo-epitopes by HLA-DRB1 molecules that carry the shared epitope (SE) sequence was proposed to explain association between HLA and seropositive RA. Although it is shown several HLA-DRB1-SE display enhanced binding affinities for ligands, ability other present epitopes has not been investigated in a systematic manner. To better understand HLA-RA connection, we aimed investigate if capacity arginine-to-citrulline-converted peptides unique HLA-SE alleles. We...
A functional epistatic interaction between susceptible HLAs provides a molecular basis for the contribution of HLA-DQ8 transdimer.
Peptide binding to class II MHC protein is commonly viewed as a combination of discrete anchor residue preferences for pockets 1, 4, 6/7, and 9. However, previous studies have suggested cooperative effects during the peptide process. Investigation DRB1*0901 motif demonstrated clear interaction between 6 In agreement with prior studies, 1 4 exhibited preferences. Previously uncharacterized 7 accommodated wide variety residues. although it was previously reported that pocket 9 completely...
Insulin is a major target of the autoimmune response associated with destruction pancreatic beta cells in type 1 diabetes. A peptide that spans junction insulin B chain and connecting (C) proinsulin has been reported to stimulate T from humans at risk for diabetes diabetes-prone NOD mice. Here we show B24-C36 binds I-A(g7), MHC class II molecule mouse, and, after intranasal administration, induces regulatory CD4(+) that, absence CD8(+) cells, block adoptive transfer Curiously, however, did...
HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), DQ8.1 DQ2.5 major risk haplotypes. Next-generation targeted sequencing of in Swedish newly diagnosed 1- to 18 year-old patients (n = 962) control subjects 636) was used construct abbreviated DQ haplotypes, converted into amino acid (AA) residues, assessed for their associations T1D. A hierarchically organized haplotype (HOH) association analysis allowed 45 unique haplotypes be categorized seven clusters. The DQ8/9 cluster...
DRB1*08:01 (DR0801) and DRB1*11:01 (DR1101) are highly homologous alleles that have opposing effects on susceptibility to primary biliary cirrhosis (PBC). DR0801 confers risk shares a key feature with other HLA class II predispose autoimmunity: nonaspartic acid at beta57. DR1101 is associated protection from PBC, its sequence includes an aspartic To elucidate mechanism for the of these PBC susceptibility, we compared features epitopes presented by DR1101. First, identified DR0801-...
Abstract DRB4*01:01 (DRB4) is a secondary HLA-DR product that part of the high-risk DR4/DQ8 haplotype associated with type 1 diabetes (T1D). DRB4 shares considerable homology HLA-DR4 alleles predispose to autoimmunity, including DRB1*04:01 and DRB1*04:04. However, protein sequence includes distinct residues would be expected alter characteristics its binding pockets. To identify high-affinity peptides are recognized in context DRB4, we used an HLA class II tetramer-based approach epitopes...
Next-generation targeted sequencing of HLA-DRB1 and HLA-DRB3, -DRB4, -DRB5 (abbreviated as DRB345) provides high resolution functional variant positions to investigate their associations with type 1 diabetes risk autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A), ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity a result polymorphisms extended linkage disequilibrium among the loci, we applied novel recursive organizer (ROR) discover disease-associated amino acid...
BackgroundHLA-DR4, a common antigen of HLA-DRB1, has multiple subtypes that are strongly associated with risk type 1 diabetes (T1D); however, some neutral or resistant. The pathobiological mechanism HLA-DR4 remains to be elucidated.MethodsWe used population-based case-control study T1D (962 patients and 636 controls) decipher genetic associations specific residues susceptibility T1D. Using birth cohort 7865 children periodically measured islet autoantibodies (GADA, IAA IA-2A), we proposed...