1 American Journal of Therapeutics 12:534 (2005) TARGETING T LYMPHOCYTES FOR IMMUNE MONITORING AND INTERVENTION IN AUTOIMMUNE DIABETES

Recognition of a peptide-MHC complex by the T cell receptor (TCR) is a key interaction which initiates T lymphocyte activation or silencing during an immune response. Fluorochrome-labeled recombinant MHC Class II-peptide reagents function as soluble mimetics of this interaction, bind to their specific TCR, and allow for detection of antigen-specific CD4+ T cells. These reagents are now under scrutiny for “immune staging ” of patients at risk for type 1 diabetes, in an effort to diagnose islet autoimmunity early enough to block immune-mediated ∃ cell destruction. Several issues are currently being addressed to improve the performance of these T cell assays: enrichment steps for better sensitivity, multiplexing of several islet epitopes, simultaneous monitoring of CD4+ and CD8+ responses, detection of low avidity T cells, combination of quantitative (number of positive cells) and qualitative (cytokine secretion, naïve/memory phenotype) readouts. CD4+ T cells are key effectors of autoimmunity, and these MHC Class II-peptide reagents, through their signaling properties, might also provide therapeutics to block the autoimmune process at its onset, analogous to the use of OKT3(1(AlaAla) anti