Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-28
pubmed:abstractText
This study addressed an important biological question, namely how certain HLA molecules modulate the disease risk conferred by other HLA molecules. The HLA molecules under investigation were HLA-DQ8 and -DR4, the two most prevalent HLA class II alleles found in Caucasian type 1 diabetic patients. A panel of human GAD (hGAD65)-specific CD4 T-cell lines and hybridomas was generated to serve as detection reagents for evaluating the peptide occupancy of DQ8 and DR4. Results indicated that DQ8 and DR4 (0401) were able to bind the same hGAD65 peptides. The coexpression of DR4 (0401) diminished DQ8-restricted T-cell responses. In addition, we also demonstrated that the diminished T-cell response varied according to the specific DRB1*04 alleles. Taken together, this study provides evidence that DR4 is able to modulate DQ8-restricted T-cell responses, possibly by competing for peptides. Given that DQ8 is a primary genetic determinant of type 1 diabetes, the decreased DQ8-restricted CD4 T-cell activity due to peptide competition may be the mechanism explaining the modulation effect of DR4 to type 1 diabetes susceptibility.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3455-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Modulatory role of DR4- to DQ8-restricted CD4 T-cell responses and type 1 diabetes susceptibility.
pubmed:affiliation
Rangos Research Center, Children's Hospital of Pittsburgh, 3460 5th Ave., Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural