التفاصيل البيبلوغرافية
| العنوان: |
Changes in autoreactive T cell avidity during type 1 diabetes development |
| المؤلفون: |
Standifer, Nathan E.1,2 NStand@benaroyaresearch.org, Burwell, Emily A.1, Gersuk, Vivian H.1, Greenbaum, Carla J.1, Nepom, Gerald T.1,2 |
| المصدر: |
Clinical Immunology. Sep2009, Vol. 132 Issue 3, p312-320. 9p. |
| مصطلحات موضوعية: |
*T cells, *DIABETES, *LYMPHOCYTE transformation, *IMMUNOSPECIFICITY, *IMMUNE response, *MOLECULE-molecule collisions, *GLUTAMATE decarboxylase, *AUTOANTIBODIES, *BINDING sites |
| مستخلص: |
Abstract: The activation threshold for antigen-specific T cell responses is dependent on the avidity of the trimolecular interaction between TCR, antigen, and MHC. We compared CD4+ T cell avidities for the diabetes-associated autoantigen glutamic acid decarboxylase 555–567 (GAD 555) among serial samples from autoantibody-positive subjects at high risk of progression to type 1 diabetes (T1D). T cells from three at-risk subjects demonstrated significant avidity increases (p <0.05 by F test) over time. This avidity shift correlated with the outgrowth of T cells expressing TCR BV 9, 15, 17 or 20 that demonstrated higher GAD 555 tetramer-binding levels compared to cells expressing other TCR BV genes. Similar analysis of autoantibody-negative, first-degree relatives and T1D patients did not demonstrate similar changes in avidity. These data implicate the outgrowth of T cells expressing higher affinity TCR in a process of antigen-specific T cell avidity maturation during the pre-clinical stage of T1D. [Copyright &y& Elsevier] |
| قاعدة البيانات: |
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