Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-2-16
|
| pubmed:abstractText |
Early exposure to cow milk proteins was linked to the development of type I diabetes by consistent epidemiology, and by feeding and tolerization studies in diabetes-prone rodents. Dietary BSA was suggested as the culprit because patients and relevant rodents have elevated anti-BSA Abs that precipitate the recently cloned protein, p69, from beta cell lysates. A total of 68 of 78 children with recent onset diabetes had BSA-reactive T cells at the time of diagnosis. Here we 1) map the fine specificity of these T cells, 2) delineate a homologous peptide sequence near the N-terminus of p69, and 3) demonstrate T cell recognition of this p69 sequence (T cell epitope p69, Tep69) by patient T cells. The Tep69 sequence is conserved in p69 of patients and diabetes-prone rodents. Whereas BSA triggers T cell proliferation, recombinant p69 and a synthetic Tep69 peptide induce early stages of T cell activation (IL-2R transcription) but insufficient IL-2 production and thus anergy. Exogenous IL-2 overrides anergy and allows proliferative expansion of p69-responsive T cells. In mixing experiments, p69 and Tep69 peptide prevented proliferative responses to BSA even at 100-fold smaller concentrations. These findings imply that high-affinity self-peptide triggers anergy, whereas low-affinity mimicry Ag triggers proliferative expansion of these T cells. This implies a disease model in which mimicry Ag would rescue autoreactive cells from ablation by self-Ag.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/ICA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, Bovine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
154
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1461-9
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:7822811-Adolescent,
pubmed-meshheading:7822811-Amino Acid Sequence,
pubmed-meshheading:7822811-Autoantigens,
pubmed-meshheading:7822811-Base Sequence,
pubmed-meshheading:7822811-Blotting, Western,
pubmed-meshheading:7822811-Child,
pubmed-meshheading:7822811-Clonal Anergy,
pubmed-meshheading:7822811-Cross Reactions,
pubmed-meshheading:7822811-Diabetes Mellitus, Type 1,
pubmed-meshheading:7822811-Female,
pubmed-meshheading:7822811-Humans,
pubmed-meshheading:7822811-Islets of Langerhans,
pubmed-meshheading:7822811-Lymphocyte Activation,
pubmed-meshheading:7822811-Male,
pubmed-meshheading:7822811-Molecular Sequence Data,
pubmed-meshheading:7822811-Receptors, Interleukin-2,
pubmed-meshheading:7822811-Recombinant Proteins,
pubmed-meshheading:7822811-Serum Albumin, Bovine,
pubmed-meshheading:7822811-T-Lymphocytes,
pubmed-meshheading:7822811-Transcription, Genetic
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
T cell activation and anergy to islet cell antigen in type I diabetes.
|
| pubmed:affiliation |
Hospital For Sick Children, Research Institute, University of Toronto, Ontario, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|