Linked Life Data

14624760

Source:http://linkedlifedata.com/resource/pubmed/id/14624760

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-11-19
pubmed:abstractText
The related tyrosine phosphatase-like proteins (PTP) IA-2 and IA-2beta are autoantigens of type 1 diabetes. Autoantibodies are predominantly against IA-2. We utilized the close homology between IA-2 and IA-2beta PTP domains to design chimeras and mutants in order to identify humoral IA-2-specific epitopes. Fifteen sera with antibodies to IA-2 specific PTP domain epitopes were tested against IA-2beta(741-848)/IA-2(795-889)/IA-2beta(943-1033), IA-2beta(741-848)/IA-2(795-845)/IA-2beta(900-1033), and IA-2beta(741-898)/IA-2(845-875)/IA-2beta(930-1033)chimeras. Two sera bound IA-2beta(741-848)/IA-2(795-889)/IA-2beta(943-1033)and IA-2beta(741-848)/IA-2(795-845)/IA-2beta(900-1033)only indicating that the IA-2 specific residues 859, 862, and/or 867 were critical for antibody binding. Mutation of glutamine 862 abolished binding in one of these sera. Seven sera bound only the IA-2beta(741-848)/IA-2(795-889)/IA-2beta(943-1033)chimera, indicating that binding required IA-2 specific amino acids within both 795-845 and 846-875, or that IA-2 residues 876-888 were important for binding. Mutation of glutamine 862 abolished binding in two of these sera, and mutation of residues 876, 877, 878, and 880 markedly reduced binding in two others. Six sera bound all three chimeras indicating that they contained multiple IA-2 specific PTP domain antibodies. In three of these sera, mutation of residues at positions 876, 877, 878, 880, and/or residues 862 and 822 reduced antibody binding by more than 50%. These findings indicate that glutamine at position 862, and residues 876-880 of the WPD loop of IA-2 are important for several of the IA-2 specific PTP domain epitopes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0896-8411
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-82
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14624760-Adolescent, pubmed-meshheading:14624760-Adult, pubmed-meshheading:14624760-Antibody Specificity, pubmed-meshheading:14624760-Autoantibodies, pubmed-meshheading:14624760-Autoantigens, pubmed-meshheading:14624760-Child, pubmed-meshheading:14624760-Child, Preschool, pubmed-meshheading:14624760-Diabetes Mellitus, pubmed-meshheading:14624760-Epitope Mapping, pubmed-meshheading:14624760-Epitopes, pubmed-meshheading:14624760-Female, pubmed-meshheading:14624760-Humans, pubmed-meshheading:14624760-Infant, pubmed-meshheading:14624760-Male, pubmed-meshheading:14624760-Membrane Proteins, pubmed-meshheading:14624760-Mutation, pubmed-meshheading:14624760-Protein Structure, Tertiary, pubmed-meshheading:14624760-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:14624760-Protein Tyrosine Phosphatases, pubmed-meshheading:14624760-Receptor-Like Protein Tyrosine Phosphatases, Class 8
pubmed:year
2003
pubmed:articleTitle
Fine mapping of diabetes-associated IA-2 specific autoantibodies.
pubmed:affiliation
Department of Medicine, Istituto Scientifico San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't