Detection of CD4⁺ Autoreactive T Cells in T1D Using HLA Class II Tetramers

The use of soluble class II MHC tetramers has enabled the identification of autoantigen-specific T cells in the peripheral blood of type 1 diabetes patients. Our approach takes advantage of the appearance of highly activated T cells expressing a CD25(+)/CD4(high+) phenotype induced by immobilized class II MHC monomer containing the GAD65 peptide. Almost all T cells that stain with the specific tetramer reside in this population and, since this activation profile is not present in normal subjects, it may provide a useful tool for analysis of the T cell response in autoimmune diabetes. The utilization of tetramer techniques in the detection of autoreactive T cells is a powerful tool to gain insight into mechanisms of the molecular basis of autoimmunity. The phenotyping of T cells should provide useful markers for progression of immune-mediated beta cell reactivity and can be utilized in clinical trials to evaluate the efficacy of the immunomodulatory therapies targeting intervention/prevention of autoimmune diseases.